rs875725

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.3345A>G(p.Glu1115Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,613,868 control chromosomes in the GnomAD database, including 404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 120 hom., cov: 32)

Exomes 𝑓: 0.014 ( 284 hom. )

Consequence

MYH9
NM_002473.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.392

Publications

10 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: G2P, Labcorp Genetics (formerly Invitae)
macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
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=-0.64).

BP6

Variant 22-36295645-T-C is Benign according to our data. Variant chr22-36295645-T-C is described in ClinVar as Benign. ClinVar VariationId is 44558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.392 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0719 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH9	NM_002473.6	MANE Select	c.3345A>G	p.Glu1115Glu	synonymous	Exon 26 of 41	NP_002464.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MYH9	ENST00000216181.11	TSL:1 MANE Select	c.3345A>G	p.Glu1115Glu	synonymous	Exon 26 of 41	ENSP00000216181.6
MYH9	ENST00000685801.1		c.3408A>G	p.Glu1136Glu	synonymous	Exon 27 of 42	ENSP00000510688.1
MYH9	ENST00000459960.1	TSL:2	n.554A>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0310

AC:

4717

AN:

152112

Hom.:

120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0742

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0250

Gnomad ASJ

AF:

0.0208

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00829

Gnomad FIN

AF:

0.0185

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.0296

GnomAD2 exomes

AF:

0.0168

AC:

4205

AN:

250798

AF XY:

0.0153

show subpopulations

Gnomad AFR exome

AF:

0.0742

Gnomad AMR exome

AF:

0.0154

Gnomad ASJ exome

AF:

0.0200

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0183

Gnomad NFE exome

AF:

0.0129

Gnomad OTH exome

AF:

0.0235

GnomAD4 exome

AF:

0.0144

AC:

21011

AN:

1461638

Hom.:

284

Cov.:

AF XY:

0.0140

AC XY:

10190

AN XY:

727106

show subpopulations

African (AFR)

AF:

0.0781

AC:

2614

AN:

33478

American (AMR)

AF:

0.0156

AC:

696

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0193

AC:

503

AN:

26128

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00936

AC:

807

AN:

86228

European-Finnish (FIN)

AF:

0.0187

AC:

996

AN:

53252

Middle Eastern (MID)

AF:

0.0780

AC:

450

AN:

5766

European-Non Finnish (NFE)

AF:

0.0124

AC:

13790

AN:

1111978

Other (OTH)

AF:

0.0191

AC:

1154

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

1224

2448

3671

4895

6119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

562

1124

1686

2248

2810

<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:

0.0310

AC:

4722

AN:

152230

Hom.:

120

Cov.:

AF XY:

0.0305

AC XY:

2270

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0741

AC:

3078

AN:

41520

American (AMR)

AF:

0.0250

AC:

383

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0208

AC:

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.00808

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0185

AC:

196

AN:

10616

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0127

AC:

865

AN:

68022

Other (OTH)

AF:

0.0293

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

233

466

698

931

1164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0238

Hom.:

144

Bravo

AF:

0.0329

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0154

EpiControl

AF:

0.0153

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

not specified (3)

Atypical hemolytic-uremic syndrome (1)

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

-0.64

CADD

Benign

7.4

(source)

DANN

Benign

0.63

PhyloP100

0.39

Mutation Taster

=100/0

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

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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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over