rs2272571

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_016239.4(MYO15A):c.6052G>A(p.Gly2018Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,581,876 control chromosomes in the GnomAD database, including 20,908 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2502 hom., cov: 33)

Exomes 𝑓: 0.14 ( 18406 hom. )

Consequence

MYO15A
NM_016239.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.25

Variant links:

Genes affected

MYO15A (HGNC:7594): (myosin XVA) This gene encodes an unconventional myosin. This protein differs from other myosins in that it has a long N-terminal extension preceding the conserved motor domain. Studies in mice suggest that this protein is necessary for actin organization in the hair cells of the cochlea. Mutations in this gene have been associated with profound, congenital, neurosensory, nonsyndromal deafness. This gene is located within the Smith-Magenis syndrome region on chromosome 17. Read-through transcripts containing an upstream gene and this gene have been identified, but they are not thought to encode a fusion protein. Several alternatively spliced transcript variants have been described, but their full length sequences have not been determined. [provided by RefSeq, Jul 2008]

MYO15A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.0833855E-5).

BP6

Variant 17-18143875-G-A is Benign according to our data. Variant chr17-18143875-G-A is described in ClinVar as [Benign]. Clinvar id is 45754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-18143875-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO15A	NM_016239.4 link	c.6052G>A	p.Gly2018Arg	missense_variant	Exon 28 of 66	ENST00000647165.2	NP_057323.3	Q9UKN7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO15A	ENST00000647165.2 link	c.6052G>A	p.Gly2018Arg	missense_variant	Exon 28 of 66		NM_016239.4	ENSP00000495481.1		Q9UKN7-1

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24172

AN:

152100

Hom.:

2495

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.262

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.508

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.181

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.155

GnomAD3 exomes

AF:

0.192

AC:

37975

AN:

198172

Hom.:

5235

AF XY:

0.181

AC XY:

19371

AN XY:

106902

show subpopulations

Gnomad AFR exome

AF:

0.150

Gnomad AMR exome

AF:

0.356

Gnomad ASJ exome

AF:

0.111

Gnomad EAS exome

AF:

0.508

Gnomad SAS exome

AF:

0.157

Gnomad FIN exome

AF:

0.172

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.155

GnomAD4 exome

AF:

0.141

AC:

201600

AN:

1429658

Hom.:

18406

Cov.:

AF XY:

0.141

AC XY:

99713

AN XY:

708132

show subpopulations

Gnomad4 AFR exome

AF:

0.144

Gnomad4 AMR exome

AF:

0.340

Gnomad4 ASJ exome

AF:

0.114

Gnomad4 EAS exome

AF:

0.495

Gnomad4 SAS exome

AF:

0.158

Gnomad4 FIN exome

AF:

0.174

Gnomad4 NFE exome

AF:

0.118

Gnomad4 OTH exome

AF:

0.159

GnomAD4 genome

AF:

0.159

AC:

24186

AN:

152218

Hom.:

2502

Cov.:

AF XY:

0.168

AC XY:

12482

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.147

Gnomad4 AMR

AF:

0.263

Gnomad4 ASJ

AF:

0.112

Gnomad4 EAS

AF:

0.507

Gnomad4 SAS

AF:

0.167

Gnomad4 FIN

AF:

0.181

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.123

Hom.:

3086

Bravo

AF:

0.167

TwinsUK

AF:

0.117

AC:

434

ALSPAC

AF:

0.113

AC:

434

ESP6500AA

AF:

0.137

AC:

566

ESP6500EA

AF:

0.115

AC:

967

ExAC

AF:

0.157

AC:

18807

Asia WGS

AF:

0.299

AC:

1039

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

May 09, 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. -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Gly2018Arg in Exon 28 of MYO15A: This variant is not expected to have clinical s ignificance because it has been identified in 13.7% (472/3448) of African Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs2272571). -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: 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 recessive nonsyndromic hearing loss 3

Benign:1

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.8

DANN

Benign

0.73

DEOGEN2

Benign

0.0022

T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0070

LIST_S2

Benign

0.52

T;.;T

MetaRNN

Benign

0.000091

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.7

.;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

3.1

.;N;.

REVEL

Benign

0.17

Sift

Benign

1.0

.;T;.

Sift4G

Benign

1.0

T;T;.

Polyphen

0.0

.;B;B

Vest4

0.059

MutPred

0.23

Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);

ClinPred

0.00029

GERP RS

2.7

Varity_R

0.029

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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