Monogenic hearing loss

Gene: SNAI2

I don't know

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 3 Mar 2022, 1:19 p.m. | Last Modified: 3 Mar 2022, 1:19 p.m.

Panel Version: 2.221

Comment on list classification: Leaving this gene as green for now, but it should be reviewed by the GMS due to the fact that only two cases have been reported of homozygous deletions in patients with Waardenburg syndrome, type 2D. Those reported with heterozygous variants either have no hearing loss or the variants have an allele frequency > 0.001 in the ExAC_EAS database.

Created: 4 Nov 2020, 2:24 p.m. | Last Modified: 4 Nov 2020, 2:24 p.m.

Panel Version: 2.102

Associated with Waardenburg syndrome, type 2D #608890 (AR) in OMIM, and Waardenburg syndrome (MONDO_0018094) in ClinGen (limited, assessed in 2017). This syndrome is characterized by deafness and pigmentary abnormalities.
SNAI2 is also know has SLUG.

Some reports of heterozygous variants associated with piebaldism (PMID: 12955764, PMID: 24443330) but no hearing loss.

PMID: 30936914 - Li et al 2019 - screened 90 patients with WS by NGS and found 2 patients with WS type 2 with de novo SNAI2 variants (c.230C>G, p. S77C and c.365C>T, p.A122V), however these variants were found at a frequency >1/10000 in the Exac population database (0.0045 and 0.0015 respectively). Presume these variants are heterozygous as they are de novo.

PMID: 12444107 - Sanchez-Martin et al 2002 - screened 38 unrelated patients with features of WS for SLUG genomic rearrangements, deletions or point mutations and found two unrelated (Bangladeshi and Dutch origin) patients with WS2 that have homozygous deletions spanning the entire SLUG coding region.

Created: 4 Nov 2020, 2:10 p.m. | Last Modified: 4 Nov 2020, 2:16 p.m.

Panel Version: 2.101

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Waardenburg syndrome, type 2D; Waardenburg syndrome type 2 MONDO_0019517

Publications

• 30936914
• 12444107

I don't know

Two families reported initially with homozygous deletion of this gene and features of Waardenburg syndrome including deafness. Additional individuals reported as part of a large Chinese cohort. Gene-disease association rated as LIMITED by ClinGen.

Created: 29 Jan 2020, 7 a.m. | Last Modified: 29 Jan 2020, 7 a.m.

Panel Version: 2.4

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Waardenburg syndrome, type 2D, MIM# 608890

Publications

• 12444107
• 30936914

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
#172800:Piebaldism[Piebaldism; White forelock; Absent pigmentation of medial forehead, eyebrows and chin; Absent pigmentation of ventral chest, abdomen and limbs; Hyperpigmented borders of unpigmented areas; Heterochromia iridis; Frequent epitheliomas; Occasional deafness; Rare Hirschsprung disease]; #608890:Waardenburg syndrome, type 2D[Congenital sensorineural deafness; Dystopia canthorum absentHeterochromia iridis]

Publications

• PMID:10518215
• 12149208
• 12444107
• 12955764
• 15691760
• 16142232
• 16286009
• 17905753
• 21512031
• 24443330
• 26331542
• 7513443
• 9182671
• 9337409
• 9721220

Comment on list classification: Good evidence from expert reviewer and OMIM

Created: 31 Jan 2016, 7:58 p.m.

Green List (high evidence)

Good evidence for causing Waardenburg syndrome (rare cause) and the diagnosis could be missed so put on green list.

Created: 19 Oct 2015, 6:10 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

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