Variant: NM_206933.3(USH2A):c.7167C>T (p.Ser2389=)

CA1394924

681822 (ClinVar)

Gene: USH2A

Condition: Usher syndrome

Inheritance Mode: Autosomal recessive inheritance

UUID: 0f97b706-2a00-4fce-8bbe-6744fe0a63bc

HGVS expressions

NM_206933.3:c.7167C>T
NM_206933.3(USH2A):c.7167C>T (p.Ser2389=)
NC_000001.11:g.215934749G>A
CM000663.2:g.215934749G>A
NC_000001.10:g.216108091G>A
CM000663.1:g.216108091G>A
NC_000001.9:g.214174714G>A
NG_009497.1:g.493648C>T
NG_009497.2:g.493700C>T
NM_206933.2:c.7167C>T
NM_206933.4:c.7167C>T
ENST00000307340.7:c.7167C>T

Likely Benign

• Met criteria codes: BS1_Supporting BP7 BP4

Expert Panel

Hearing Loss VCEP

Criteria Specification Information

Evidence submitted by expert panel

Hearing Loss VCEP

The filtering allele frequency (the lower threshold of the 95% CI of 57/19928 of the c.7167C>T (p.Ser2389=) variant in the USH2A gene is 0.22% for East Asian chromosomes by gnomAD v2.1.1, which is a higher frequency than would be expected for an autosomal recessive pathogenic variant based on the thresholds defined by the ClinGen Hearing Loss Expert Panel (BS1_Supporting). The silent c.7167C>T variant in USH2A is not predicted by the computational prediction analysis using MaxEntScan to impact splicing (BP4, BP7). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BS1_P, BP4,BP7.

Met criteria codes

• BS1_Supporting: The filtering AF (95% CI) is 0.22% (57/19928) of East Asian chromosomes in gnomAD v2.1.1 and 0.22% (12/3114) of South Asian chromosomes in gnomAD v3.
• BP7: no splicing impact predicted by MaxEntScan and other splicing predictors in Alamut.
• BP4: Residue is not highly conserved and no splicing impact predicted by MaxEntScan and other splicing predictors in Alamut.

Approved on: 2020-05-26

Published on: 2020-05-26