22-36288285-C-T

Position:

chr22-36288285-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002473.6(MYH9):c.4899G>A(p.Arg1633=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0538 in 1,614,018 control chromosomes in the GnomAD database, including 2,962 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.072 ( 469 hom., cov: 33)

Exomes 𝑓: 0.052 ( 2493 hom. )

Consequence

MYH9
NM_002473.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.725

Variant links:

Genes affected

MYH9 (HGNC:7579): (myosin heavy chain 9) This gene encodes a conventional non-muscle myosin; this protein should not be confused with the unconventional myosin-9a or 9b (MYO9A or MYO9B). The encoded protein is a myosin IIA heavy chain that contains an IQ domain and a myosin head-like domain which is involved in several important functions, including cytokinesis, cell motility and maintenance of cell shape. Defects in this gene have been associated with non-syndromic sensorineural deafness autosomal dominant type 17, Epstein syndrome, Alport syndrome with macrothrombocytopenia, Sebastian syndrome, Fechtner syndrome and macrothrombocytopenia with progressive sensorineural deafness. [provided by RefSeq, Dec 2011]

MYH9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 22-36288285-C-T is Benign according to our data. Variant chr22-36288285-C-T is described in ClinVar as [Benign]. Clinvar id is 44566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36288285-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.725 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH9	NM_002473.6 linkuse as main transcript	c.4899G>A	p.Arg1633=	synonymous_variant	34/41	ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11 linkuse as main transcript	c.4899G>A	p.Arg1633=	synonymous_variant	34/41	1	NM_002473.6	ENSP00000216181	P1	P35579-1
MYH9	ENST00000685801.1 linkuse as main transcript	c.4962G>A	p.Arg1654=	synonymous_variant	35/42			ENSP00000510688
MYH9	ENST00000691109.1 linkuse as main transcript	n.5194G>A		non_coding_transcript_exon_variant	28/35

Frequencies

GnomAD3 genomes

AF:

0.0724

AC:

11013

AN:

152102

Hom.:

468

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.0176

Gnomad AMR

AF:

0.0866

Gnomad ASJ

AF:

0.0380

Gnomad EAS

AF:

0.0914

Gnomad SAS

AF:

0.0728

Gnomad FIN

AF:

0.0598

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0434

Gnomad OTH

AF:

0.0665

GnomAD3 exomes

AF:

0.0714

AC:

17958

AN:

251380

Hom.:

834

AF XY:

0.0680

AC XY:

9236

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.133

Gnomad ASJ exome

AF:

0.0475

Gnomad EAS exome

AF:

0.0986

Gnomad SAS exome

AF:

0.0786

Gnomad FIN exome

AF:

0.0652

Gnomad NFE exome

AF:

0.0435

Gnomad OTH exome

AF:

0.0627

GnomAD4 exome

AF:

0.0519

AC:

75800

AN:

1461798

Hom.:

2493

Cov.:

AF XY:

0.0523

AC XY:

38017

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.125

Gnomad4 AMR exome

AF:

0.127

Gnomad4 ASJ exome

AF:

0.0445

Gnomad4 EAS exome

AF:

0.0940

Gnomad4 SAS exome

AF:

0.0760

Gnomad4 FIN exome

AF:

0.0675

Gnomad4 NFE exome

AF:

0.0426

Gnomad4 OTH exome

AF:

0.0536

GnomAD4 genome

AF:

0.0724

AC:

11017

AN:

152220

Hom.:

469

Cov.:

AF XY:

0.0720

AC XY:

5359

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.120

Gnomad4 AMR

AF:

0.0863

Gnomad4 ASJ

AF:

0.0380

Gnomad4 EAS

AF:

0.0910

Gnomad4 SAS

AF:

0.0718

Gnomad4 FIN

AF:

0.0598

Gnomad4 NFE

AF:

0.0434

Gnomad4 OTH

AF:

0.0658

Alfa

AF:

0.0513

Hom.:

321

Bravo

AF:

0.0774

Asia WGS

AF:

0.0690

AC:

238

AN:

3478

EpiCase

AF:

0.0416

EpiControl

AF:

0.0402

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Arg1633Arg in Exon 34 of MYH9: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 11.1% (414/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs5756130). -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal dominant nonsyndromic hearing loss 17

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

MYH9-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.7

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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