NM_000260.4(MYO7A):c.1849T>C (p.Ser617Pro) AND Autosomal recessive nonsyndromic hearing loss 2

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: May 22, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000681537.2

Allele description [Variation Report for NM_000260.4(MYO7A):c.1849T>C (p.Ser617Pro)]

NM_000260.4(MYO7A):c.1849T>C (p.Ser617Pro)

Gene:

MYO7A:myosin VIIA [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.5

Genomic location:

Preferred name:

NM_000260.4(MYO7A):c.1849T>C (p.Ser617Pro)

Other names:

NM_000260.4(MYO7A):c.1849T>C

HGVS:

NC_000011.10:g.77172799T>C
NG_009086.2:g.49554T>C
NM_000260.4:c.1849T>CMANE SELECT
NM_001127180.2:c.1849T>C
NM_001369365.1:c.1816T>C
NP_000251.3:p.Ser617Pro
NP_001120652.1:p.Ser617Pro
NP_001356294.1:p.Ser606Pro
LRG_1420t1:c.1849T>C
LRG_1420:g.49554T>C
LRG_1420p1:p.Ser617Pro
NC_000011.9:g.76883845T>C
NC_000011.9:g.76883845T>C
NG_009086.1:g.49536T>C
NM_000260.3(MYO7A):c.1849T>C
NM_000260.3:c.1849T>C
NM_001127180.1:c.1849T>C
p.Ser617Pro

Protein change:

S606P

Links:

dbSNP: rs782063761

NCBI 1000 Genomes Browser:

rs782063761

Molecular consequence:

NM_000260.4:c.1849T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127180.2:c.1849T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001369365.1:c.1816T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Autosomal recessive nonsyndromic hearing loss 2
Synonyms:: NEUROSENSORY NONSYNDROMIC RECESSIVE DEAFNESS 2; Deafness, autosomal recessive 2
Identifiers:: MONDO: MONDO:0010807; MedGen: C1838701; Orphanet: 90636; OMIM: 600060

Recent activity

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PI4KAP1 phosphatidylinositol 4-kinase alpha pseudogene 1 [Homo sapiens]
PI4KAP1 phosphatidylinositol 4-kinase alpha pseudogene 1 [Homo sapiens]
Gene ID:728233

Gene
GGT3P gamma-glutamyltransferase 3 pseudogene [Homo sapiens]
GGT3P gamma-glutamyltransferase 3 pseudogene [Homo sapiens]
Gene ID:2679

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000807729	National Institute on Deafness and Communication Disorders, National Institutes of Health	no assertion criteria provided	Pathogenic (Jul 5, 2018)	germline	research
SCV002521242	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 22, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28041643, 33187236, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000807729

National Institute on Deafness and Communication Disorders, National Institutes of Health

no assertion criteria provided

Pathogenic
(Jul 5, 2018)

germline

research

SCV002521242

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 22, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	2	not provided	not provided	2	yes	research, clinical testing

Citations

PubMed

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.

Carss KJ, Arno G, Erwood M, Stephens J, Sanchis-Juan A, Hull S, Megy K, Grozeva D, Dewhurst E, Malka S, Plagnol V, Penkett C, Stirrups K, Rizzo R, Wright G, Josifova D, Bitner-Glindzicz M, Scott RH, Clement E, Allen L, Armstrong R, Brady AF, et al.

Am J Hum Genet. 2017 Jan 5;100(1):75-90. doi: 10.1016/j.ajhg.2016.12.003. Epub 2016 Dec 29.

PubMed [citation]

PMID:: 28041643
PMCID:: PMC5223092

Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families.

Doll J, Vona B, Schnapp L, Rüschendorf F, Khan I, Khan S, Muhammad N, Alam Khan S, Nawaz H, Khan A, Ahmad N, Kolb SM, Kühlewein L, Labonne JDJ, Layman LC, Hofrichter MAH, Röder T, Dittrich M, Müller T, Graves TD, Kong IK, Nanda I, et al.

Genes (Basel). 2020 Nov 11;11(11). doi:pii: E1329. 10.3390/genes11111329.

PubMed [citation]

PMID:: 33187236
PMCID:: PMC7709052

See all PubMed Citations (3)

Details of each submission

From National Institute on Deafness and Communication Disorders, National Institutes of Health, SCV000807729.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	yes	research	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

From 3billion, SCV002521242.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (3)

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.92; 3Cnet: 0.86). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with MYO7A related disorder (ClinVar ID: VCV000438172 / PMID: 28041643). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 33187236) and co-segregate with the disease in at least one similarly affected relative/individual in the same family or similarly affected unrelated family (PMID: 33187236). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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