Amelogenesis imperfecta

Gene: SMARCD2

I don't know

Comment on list classification: While there are several cases reported with biallelic SMARCD2 variants and a 'dental' phenotype, the symptoms are very mild and they do not fit into the scope of this panel. Hence, this gene should remain Amber for Amelogenesis imperfecta until more evidence emerges.

Created: 2 Jan 2026, 3:45 p.m. | Last Modified: 2 Jan 2026, 3:45 p.m.

Panel Version: 4.25

PMID:36135322 Ibrahim et al., 2022
Report of a 12-year-old African American girl with 'autosomal recessive congenital neutropenia with specific granulocytes deficiency' - compound heterozygous variants c.1081del, (p.Gln361Argfs*15) and c.217C>T (p.Arg73*) in SMARCD2 - rare in gnomAD v4.1., no homozygotes. Phenotype: severe congenital neutropenia, recurrent infections, bilateral cervical and submandibular lymphadenopathy, gingival hypertrophy, and chronic stomatitis “cauliflower ear” deformity. Seq method: clinical exome sequencing.

PMID: 33279574 van der Loeff et al., 2021
Female patient, consanguineous parents; homozygous variant at SMARCD2 c.1181+1G>A - not in gnomAD v4.1.
Phenotype: presented at 1 month with poor feeding, weight loss, a sublingual ulcer, and delayed cord separation with omphalitis. She also had misaligned teeth and brittle nails. Seq method: WES.

PMID: 33025377 Yucel et al., 2020
11-year-old female patient with a variety of infections including sepsis, deep tissue abscesses, otitis, pneumonia, gingivitis, and diarrhea since infancy. Homozygous for c.93del, p.Ala32Argfs*80 in SMARCD2 - rare, no homozygotes in gnomAD v4.1. Seq method: 'targeted NGS'.

PMID:28369036 Witzel et al., 2017
Reported three independent consanguineous pedigrees with four patients. Common phenotype: delayed separation of umbilical cord, severe bacterial infections associated with neutropenia, parasitosis, or chronic diarrhoea; mild-to-moderate developmental delay and dysmorphic features; misaligned, dysplastic teeth and 'incomplete' amelogenesis imperfecta; brittle nails.
Variants identified in SMARCD2: c.1181+1G>A; c.414_438dup, p.Gln147Glufs*5; c.401+2T>C - variants not present in gnomAD v4.1. Seq method: WES.

This gene is associated with AR Specific granule deficiency 2, OMIM:617475 (accessed 11th Nov 2025).

Created: 10 Nov 2025, 3:18 p.m. | Last Modified: 10 Nov 2025, 3:18 p.m.

Panel Version: 4.19

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Specific granule deficiency 2, OMIM:617475

Publications

• 28369036
• 33025377
• 33279574
• 36135322

I don't know

PMID:33279574 reported one individual with a homozygous SMARCD2 variant. Phenotype included many features but tooth phenotype was:
Irregularly shaped misaligned teeth (partly conical)

PMID:28369036 reported three pedigrees with homozygous SMARCD2 variants. Phenotype included many features but tooth phenotype was: misaligned, dysplastic teeth and incomplete amelogenesis imperfecta

PMID:33025377 describe oral phenotype as bruxism

PMID:36135322 describe oral phenotype as gingival hypertrophy but present photos where teeth are visible but it's difficult to judge whether there is or isn't AI.

I would place as amber.

Created: 17 Jul 2025, 12:30 p.m. | Last Modified: 17 Jul 2025, 12:30 p.m.

Panel Version: 4.5

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
many including Amelogenesis imperfecta

Publications

• PMID: 33279574
• 28369036
• 33025377
• 36135322

Witzel et al. (2017, PMID:28369036) reported 4 patients from 3 unrelated consanguineous families with SGD2. 2 unrelated patients had additional features, including incomplete amelogenesis. They identified distinct segregating homozygous mutations in SMARCD2 in all three pedigrees.

Created: 12 Jun 2017, 9:10 a.m.