rs201738304

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002473.6(MYH9):c.705+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,613,476 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 6 hom. )

Consequence

MYH9
NM_002473.6 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.25

Publications

0 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 22-36322418-G-A is Benign according to our data. Variant chr22-36322418-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 164462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36322418-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 164462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36322418-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 164462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36322418-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 164462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36322418-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 164462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36322418-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 164462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36322418-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 164462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36322418-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 164462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36322418-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 164462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36322418-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 164462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36322418-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 164462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36322418-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 164462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36322418-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 164462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36322418-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 164462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36322418-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 164462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36322418-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 164462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36322418-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 164462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36322418-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 164462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36322418-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 164462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36322418-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 164462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00105 (160/152384) while in subpopulation NFE AF = 0.00193 (131/68036). AF 95% confidence interval is 0.00166. There are 1 homozygotes in GnomAd4. There are 71 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 160 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH9	NM_002473.6 link	c.705+11C>T		intron_variant	Intron 6 of 40	ENST00000216181.11	NP_002464.1	P35579-1A0A024R1N1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11 link	c.705+11C>T		intron_variant	Intron 6 of 40	1	NM_002473.6	ENSP00000216181.6		P35579-1

Frequencies

GnomAD3 genomes

AF:

0.00105

AC:

160

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00193

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00103

AC:

258

AN:

250988

AF XY:

0.00105

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00201

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.00158

AC:

2313

AN:

1461092

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

1115

AN XY:

726906

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33460

American (AMR)

AF:

0.0000224

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0000766

AC:

AN:

26124

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39696

South Asian (SAS)

AF:

0.000243

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.000489

AC:

AN:

53138

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00197

AC:

2192

AN:

1111564

Other (OTH)

AF:

0.000961

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

113

227

340

454

567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<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:

0.00105

AC:

160

AN:

152384

Hom.:

Cov.:

AF XY:

0.000953

AC XY:

AN XY:

74522

show subpopulations

African (AFR)

AF:

0.000553

AC:

AN:

41594

American (AMR)

AF:

0.000131

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00193

AC:

131

AN:

68036

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00111

Hom.:

Bravo

AF:

0.00104

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 08, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 17

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not specified

Benign:1

Feb 26, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

c.705+11C>T in intron 06 of MYH9: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence and has been identified in 0.2% (114/65762) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs368 753427). -

MYH9-related disorder

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

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.3

(source)

DANN

Benign

0.68

PhyloP100

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=100/0

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over