22-36288285-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002473.6(MYH9):c.4899G>A(p.Arg1633Arg) 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:8

Conservation

PhyloP100: -0.725

Publications

23 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss 17
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
May-Hegglin anomaly
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MYH9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 44566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002473.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH9	NM_002473.6	MANE Select	c.4899G>A	p.Arg1633Arg	synonymous	Exon 34 of 41	NP_002464.1	P35579-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYH9	ENST00000216181.11	TSL:1 MANE Select	c.4899G>A	p.Arg1633Arg	synonymous	Exon 34 of 41	ENSP00000216181.6	P35579-1
MYH9	ENST00000685801.1		c.4962G>A	p.Arg1654Arg	synonymous	Exon 35 of 42	ENSP00000510688.1	A0A8I5KWT8
MYH9	ENST00000955568.1		c.4962G>A	p.Arg1654Arg	synonymous	Exon 35 of 42	ENSP00000625627.1

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

GnomAD2 exomes

AF:

0.0714

AC:

17958

AN:

251380

AF XY:

0.0680

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 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

African (AFR)

AF:

0.125

AC:

4194

AN:

33480

American (AMR)

AF:

0.127

AC:

5682

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0445

AC:

1163

AN:

26136

East Asian (EAS)

AF:

0.0940

AC:

3731

AN:

39694

South Asian (SAS)

AF:

0.0760

AC:

6557

AN:

86256

European-Finnish (FIN)

AF:

0.0675

AC:

3601

AN:

53342

Middle Eastern (MID)

AF:

0.0550

AC:

317

AN:

5768

European-Non Finnish (NFE)

AF:

0.0426

AC:

47321

AN:

1112006

Other (OTH)

AF:

0.0536

AC:

3234

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

4359

8718

13076

17435

21794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1900

3800

5700

7600

9500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0724

AC:

11017

AN:

152220

Hom.:

469

Cov.:

AF XY:

0.0720

AC XY:

5359

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.120

AC:

4988

AN:

41524

American (AMR)

AF:

0.0863

AC:

1319

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0380

AC:

132

AN:

3472

East Asian (EAS)

AF:

0.0910

AC:

471

AN:

5174

South Asian (SAS)

AF:

0.0718

AC:

346

AN:

4820

European-Finnish (FIN)

AF:

0.0598

AC:

634

AN:

10608

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0434

AC:

2949

AN:

68014

Other (OTH)

AF:

0.0658

AC:

139

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

505

1010

1515

2020

2525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

248

372

496

620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0576

Hom.:

667

Bravo

AF:

0.0774

Asia WGS

AF:

0.0690

AC:

238

AN:

3478

EpiCase

AF:

0.0416

EpiControl

AF:

0.0402

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (3)

Autosomal dominant nonsyndromic hearing loss 17 (1)

MYH9-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.7

(source)

DANN

Benign

0.53

PhyloP100

-0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=92/8

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over