Cytopenia - NOT Fanconi anaemia

Gene: SRP72

I don't know

Comment on list classification: Several lines of conflicting evidence, including lack of relevant phenotype in mouse model, unaffected carriers and variants in other genes that could explain patient phenotypes - this means strongly corroborating evidence is required before this gene can be added to a diagnostic panel.

Created: 30 Oct 2025, 12:05 p.m. | Last Modified: 30 Oct 2025, 12:05 p.m.

Panel Version: 4.26

SRP72 variants have been associated with Bone marrow failure syndrome 1, OMIM:614675 (accessed on 30-10-2025).

- PMID: 22541560: two monoallelic variants in two unrelated families, both variants segregated with the condition and supportive functional studies were given

- PMID: 29146883: four cases were reported with SRP72 variants. Case UB043 had a >9kb deletion encompassing SRP72. SRP72 was also deleted (4.5kb) in Case UB077, however, this patient also had two pathogenic variants in the SBDS gene (c.258+2T>G and c.184A>T, p.Lys62*). Two further cases had a SRP72 variant (c.28T>A, p.Ser10Thr) together with the SBDS variants mentioned above.

- PMID: 40922878: 14yo with pruritus, pancytopenia, decreased bone marrow proliferation, low granulocyte proportion, increased erythrocyte proportion, and rare megakaryocytes. Heterozygous for c.1442_1448del, p.Ile481Thrfs*12 which was inherited from his unaffected 46yo father. This variant is absent from gnomad but there are more than 10 other NMD-predicted variants with >/=5 hets in gnomad.

- PMID: 31254415: Srp72+/- mice did not exhibit major haematological abnormalities.

Created: 30 Oct 2025, 12:05 p.m. | Last Modified: 30 Oct 2025, 12:05 p.m.

Panel Version: 4.25

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Bone marrow failure syndrome 1, OMIM:614675; autosomal dominant aplasia and myelodysplasia, MONDO:0013851

Publications

• 22541560
• 29146883
• 32098966
• 31254415
• 40922878

I don't know

Gene rating submitted by Steve Keeney Molecular Diagnostics Centre Central Manchester NHS Foundation Trust January 2019 on behalf of North West GLH for the GMS Haematology specialist test group.

Created: 18 Feb 2019, 2:55 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Inherited Bone Marrow Failure Syndromes - Aplastic Anaemia; Bone Marrow Failure, Familial; Bone marrow failure, familial, 614675; Familial Bone Marrow Failure; Familial MDS (Myelodysplastic syndromes); Bone Marrow Failure, Familial

Green List (high evidence)

Gene rating submitted by Mandy Nesbitt Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North East GLH for the GMS Haematology specialist test group.

Created: 14 Feb 2019, 5:39 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
614675 Bone marrow failure syndrome 1

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Gene rating submitted by Frances Smith Viapath Kings College Hospital February 2019 on behalf of London South GLH for the GMS Haematology specialist test group.

Created: 8 Feb 2019, 1:37 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
614675 Bone marrow failure syndrome 1

Variants in this GENE are reported as part of current diagnostic practice

I don't know

Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene Amber.

Created: 22 Jul 2019, 12:47 p.m. | Last Modified: 22 Jul 2019, 12:47 p.m.

Panel Version: 0.73

Discrepant reviews for SRP72. To be discussed at July workshop to agree rating

Created: 22 Jul 2019, 12:46 p.m. | Last Modified: 22 Jul 2019, 12:46 p.m.

Panel Version: 0.72

Initial gene list (Consensus Genes for SPEC HAEM Panels 31.01.19 North West v1 FINAL.xlsx) collated by Steve Keeney Molecular Diagnostics Centre Central Manchester NHS Foundation Trust January 2019 on behalf of North West GLH for the GMS Haematology specialist test group. Gene Symbol submitted: SRP72; Suggested initial gene rating: I don't know; Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Phenotypes: Inherited Bone Marrow Failure Syndromes - Aplastic Anaemia; Bone Marrow Failure, Familial;Bone marrow failure, familial, 614675;Familial Bone Marrow Failure;Familial MDS (Myelodysplastic syndromes);Bone Marrow Failure, Familial; PMID(s): 22541560; 29146883

Created: 18 Feb 2019, 2:57 p.m.

Initial gene list (Consensus Genes for Panels_Haem_SHEFFIELD-29.01.2019.xlsx) collated by Mandy Nesbitt Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North East GLH for the GMS Haematology specialist test group. Gene Symbol submitted: SRP72; Suggested initial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? Yes; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Phenotypes: 614675 Bone marrow failure syndrome 1; PMID(s): none submitted

Created: 14 Feb 2019, 5:40 p.m.

Initial gene list (Consensus Genes for Haem Panels 17.12.18_KCH.xlsx) collated by Frances Smith Viapath Kings College Hospital February 2019 on behalf of London South GLH for the GMS Haematology specialist test group. Gene Symbol submitted: SRP72; Suggested intial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? Yes; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Phenotypes: 614675 Bone marrow failure syndrome 1; PMID(s): 22541560

Created: 8 Feb 2019, 1:43 p.m.

Initial gene list (Consensus Genes for Panels 17.12.18_Haem_WWMGLH_v3.xlxs) collated by Carl Fratter Oxford Medical Genetics Laboratories January 2019 on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group. Gene Symbol submitted: SRP72; Suggested intial gene rating: I don't know; Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Phenotypes: Inherited Bone Marrow Failure Syndromes - Aplastic Anaemia; Bone Marrow Failure, Familial;Bone marrow failure, familial, 614675;Familial Bone Marrow Failure;Familial MDS (Myelodysplastic syndromes);Bone Marrow Failure, Familial; PMID(s): none submitted

Created: 6 Feb 2019, 3:13 p.m.

I don't know

Gene rating submitted by Carl Fratter Oxford Medical Genetics Laboratories January 2019 on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group.

Created: 6 Feb 2019, 3:12 p.m.