rs111033231

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000260.4(MYO7A):c.6640G>A(p.Gly2214Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 1,573,326 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 85 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 82 hom. )

Consequence

MYO7A
NM_000260.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 2.09

Variant links:

Genes affected

MYO7A (HGNC:7606): (myosin VIIA) This gene is a member of the myosin gene family. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. This gene encodes an unconventional myosin with a very short tail. Defects in this gene are associated with the mouse shaker-1 phenotype and the human Usher syndrome 1B which are characterized by deafness, reduced vestibular function, and (in human) retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

MYO7A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018300116).

BP6

Variant 11-77214688-G-A is Benign according to our data. Variant chr11-77214688-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 43338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77214688-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4 link	c.6640G>A	p.Gly2214Ser	missense_variant	Exon 49 of 49	ENST00000409709.9	NP_000251.3	Q13402-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYO7A	ENST00000409709.9 link	c.6640G>A	p.Gly2214Ser	missense_variant	Exon 49 of 49	1	NM_000260.4	ENSP00000386331.3	Q13402-1
MYO7A	ENST00000458637.6 link	c.6520G>A	p.Gly2174Ser	missense_variant	Exon 49 of 49	1		ENSP00000392185.2	Q13402-2
MYO7A	ENST00000409619.6 link	c.6493G>A	p.Gly2165Ser	missense_variant	Exon 50 of 50	1		ENSP00000386635.2	Q13402-8
MYO7A	ENST00000458169.2 link	c.4066G>A	p.Gly1356Ser	missense_variant	Exon 29 of 29	1		ENSP00000417017.2	H7C4D8
MYO7A	ENST00000670577.1 link	n.*1212G>A		non_coding_transcript_exon_variant	Exon 32 of 32			ENSP00000499323.1	A0A590UJ94
MYO7A	ENST00000670577.1 link	n.*1212G>A		3_prime_UTR_variant	Exon 32 of 32			ENSP00000499323.1	A0A590UJ94

Frequencies

GnomAD3 genomes

AF:

0.0175

AC:

2632

AN:

150610

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0610

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00840

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0178

GnomAD3 exomes

AF:

0.00428

AC:

813

AN:

189888

Hom.:

AF XY:

0.00330

AC XY:

334

AN XY:

101164

show subpopulations

Gnomad AFR exome

AF:

0.0579

Gnomad AMR exome

AF:

0.00430

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00221

Gnomad SAS exome

AF:

0.000330

Gnomad FIN exome

AF:

0.0000546

Gnomad NFE exome

AF:

0.000368

Gnomad OTH exome

AF:

0.00279

GnomAD4 exome

AF:

0.00206

AC:

2924

AN:

1422596

Hom.:

Cov.:

AF XY:

0.00186

AC XY:

1312

AN XY:

703990

show subpopulations

Gnomad4 AFR exome

AF:

0.0666

Gnomad4 AMR exome

AF:

0.00432

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00135

Gnomad4 SAS exome

AF:

0.000161

Gnomad4 FIN exome

AF:

0.0000392

Gnomad4 NFE exome

AF:

0.000231

Gnomad4 OTH exome

AF:

0.00563

GnomAD4 genome

AF:

0.0175

AC:

2643

AN:

150730

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

1298

AN XY:

73740

show subpopulations

Gnomad4 AFR

AF:

0.0611

Gnomad4 AMR

AF:

0.00839

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.0176

Alfa

AF:

0.00315

Hom.:

Bravo

AF:

0.0199

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0536

AC:

219

ESP6500EA

AF:

0.000600

AC:

ExAC

AF:

0.00398

AC:

476

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Oct 23, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Oct 28, 2019

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 10, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Gly2214Ser in exon 49 of MYO7A: This variant is not expected to have clinical si gnificance because this amino acid is not conserved in other species. This amino acid is a serine in elephant, platypus, chicken, lizard, frog, and stickleback. In addition, this variant has also been identified by our laboratory in ~20% of Black probands. -

not provided

Benign:3

Aug 26, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 11

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Autosomal recessive nonsyndromic hearing loss 2

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Usher syndrome type 1B

Benign:1

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Usher syndrome type 1

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Meniere disease

Benign:1

Dec 14, 2020

Otology & Neurotology- Genomics of vestibular disorders (CTS-495), Jose Antonio López Escámez, Centro Pfizer - Universidad de Granada - Junta de Andalucía de Genómica e Investigación Oncológica (GENYO)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: case-control

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.28

T;.;.;T

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.24

LIST_S2

Uncertain

0.86

D;D;D;D

MetaRNN

Benign

0.0018

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.0

N;.;.;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.46

N;N;N;N

REVEL

Benign

0.22

Sift

Benign

0.38

T;T;T;T

Sift4G

Benign

0.47

T;T;T;T

Polyphen

0.0020

B;.;.;.

Vest4

0.10

MVP

0.72

MPC

0.084

ClinPred

0.0014

GERP RS

0.0089

Varity_R

0.036

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over