rs138502859

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002473.6(MYH9):c.1158C>T(p.Thr386Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,613,820 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 11 hom. )

Consequence

MYH9
NM_002473.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.42

Publications

2 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=-0.48).

BP6

Variant 22-36318276-G-A is Benign according to our data. Variant chr22-36318276-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 164460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.42 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00126 (192/151962) while in subpopulation AMR AF = 0.00418 (64/15296). AF 95% confidence interval is 0.00336. There are 3 homozygotes in GnomAd4. There are 90 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 192 AD gene.

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.1158C>T	p.Thr386Thr	synonymous	Exon 11 of 41	NP_002464.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MYH9	ENST00000216181.11	TSL:1 MANE Select	c.1158C>T	p.Thr386Thr	synonymous	Exon 11 of 41	ENSP00000216181.6
MYH9	ENST00000685801.1		c.1158C>T	p.Thr386Thr	synonymous	Exon 11 of 42	ENSP00000510688.1
MYH9	ENST00000955568.1		c.1158C>T	p.Thr386Thr	synonymous	Exon 11 of 42	ENSP00000625627.1

Frequencies

GnomAD3 genomes

AF:

0.00126

AC:

192

AN:

151842

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000438

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00123

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00119

AC:

298

AN:

251436

AF XY:

0.00128

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.00198

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00132

Gnomad OTH exome

AF:

0.00358

GnomAD4 exome

AF:

0.00103

AC:

1504

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

784

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00146

AC:

AN:

33480

American (AMR)

AF:

0.00152

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00145

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00146

AC:

126

AN:

86258

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.0314

AC:

181

AN:

5768

European-Non Finnish (NFE)

AF:

0.000817

AC:

909

AN:

1112008

Other (OTH)

AF:

0.00217

AC:

131

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

192

289

385

481

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.00126

AC:

192

AN:

151962

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.000436

AC:

AN:

41248

American (AMR)

AF:

0.00418

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00145

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00123

AC:

AN:

68016

Other (OTH)

AF:

0.00379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00104

Hom.:

Bravo

AF:

0.00119

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00229

EpiControl

AF:

0.00213

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (7)

MYH9-related disorder (2)

Autosomal dominant nonsyndromic hearing loss 17 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

1.4

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

Other links and lift over