rs41279999

Positions:

chr22-36298908-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002473.6(MYH9):c.3100+11G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0323 in 1,613,458 control chromosomes in the GnomAD database, including 1,177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 119 hom., cov: 32)

Exomes 𝑓: 0.032 ( 1058 hom. )

Consequence

MYH9
NM_002473.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.31

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 22-36298908-C-G is Benign according to our data. Variant chr22-36298908-C-G is described in ClinVar as [Benign]. Clinvar id is 44556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36298908-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH9	NM_002473.6 link	c.3100+11G>C		intron_variant		ENST00000216181.11	NP_002464.1	P35579-1A0A024R1N1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MYH9	ENST00000216181.11 link	c.3100+11G>C	intron_variant	1	NM_002473.6	ENSP00000216181.6	P35579-1
MYH9	ENST00000685801.1 link	c.3163+11G>C	intron_variant			ENSP00000510688.1	A0A8I5KWT8
MYH9	ENST00000691109.1 link	n.3395+11G>C	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0308

AC:

4694

AN:

152162

Hom.:

118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0222

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0220

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.0981

Gnomad SAS

AF:

0.0753

Gnomad FIN

AF:

0.0568

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0270

Gnomad OTH

AF:

0.0315

GnomAD3 exomes

AF:

0.0381

AC:

9567

AN:

251260

Hom.:

294

AF XY:

0.0400

AC XY:

5440

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.0206

Gnomad AMR exome

AF:

0.0158

Gnomad ASJ exome

AF:

0.0178

Gnomad EAS exome

AF:

0.0919

Gnomad SAS exome

AF:

0.0757

Gnomad FIN exome

AF:

0.0490

Gnomad NFE exome

AF:

0.0285

Gnomad OTH exome

AF:

0.0326

GnomAD4 exome

AF:

0.0325

AC:

47433

AN:

1461178

Hom.:

1058

Cov.:

AF XY:

0.0335

AC XY:

24362

AN XY:

726924

show subpopulations

Gnomad4 AFR exome

AF:

0.0211

Gnomad4 AMR exome

AF:

0.0158

Gnomad4 ASJ exome

AF:

0.0163

Gnomad4 EAS exome

AF:

0.105

Gnomad4 SAS exome

AF:

0.0703

Gnomad4 FIN exome

AF:

0.0501

Gnomad4 NFE exome

AF:

0.0274

Gnomad4 OTH exome

AF:

0.0341

GnomAD4 genome

AF:

0.0309

AC:

4702

AN:

152280

Hom.:

119

Cov.:

AF XY:

0.0324

AC XY:

2416

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0224

Gnomad4 AMR

AF:

0.0221

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.0973

Gnomad4 SAS

AF:

0.0760

Gnomad4 FIN

AF:

0.0568

Gnomad4 NFE

AF:

0.0270

Gnomad4 OTH

AF:

0.0307

Alfa

AF:

0.0267

Hom.:

Bravo

AF:

0.0280

Asia WGS

AF:

0.0860

AC:

299

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	3100+11G>C in Intron 24 of MYH9: This variant is not expected to have clinical s ignificance because it is not located within the conserved splice consensus sequ ence and has been identified in 3.0% (208/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.wa shington.edu/EVS; dbSNP rs41279999). -

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 03, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -
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 12, 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 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.84

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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