rs148112044

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002473.6(MYH9):c.2721C>T(p.Thr907Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000723 in 1,611,744 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00040 ( 6 hom. )

Consequence

MYH9
NM_002473.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -6.05

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:

MYH9 (HGNC:):

MYH9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 22-36300968-G-A is Benign according to our data. Variant chr22-36300968-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 164445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36300968-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-6.05 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00386 (588/152288) while in subpopulation AFR AF= 0.0133 (553/41560). AF 95% confidence interval is 0.0124. There are 2 homozygotes in gnomad4. There are 283 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 588 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH9	NM_002473.6 linkuse as main transcript	c.2721C>T	p.Thr907Thr	synonymous_variant	22/41	ENST00000216181.11	NP_002464.1	P35579-1A0A024R1N1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYH9	ENST00000216181.11 linkuse as main transcript	c.2721C>T	p.Thr907Thr	synonymous_variant	22/41	1	NM_002473.6	ENSP00000216181.6	P35579-1
MYH9	ENST00000685801.1 linkuse as main transcript	c.2784C>T	p.Thr928Thr	synonymous_variant	23/42			ENSP00000510688.1	A0A8I5KWT8
MYH9	ENST00000495928.1 linkuse as main transcript	n.271C>T		non_coding_transcript_exon_variant	2/2	2
MYH9	ENST00000691109.1 linkuse as main transcript	n.3016C>T		non_coding_transcript_exon_variant	16/35

Frequencies

GnomAD3 genomes

AF:

0.00385

AC:

586

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00104

AC:

259

AN:

249676

Hom.:

AF XY:

0.000740

AC XY:

100

AN XY:

135128

show subpopulations

Gnomad AFR exome

AF:

0.0138

Gnomad AMR exome

AF:

0.000838

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000396

AC:

578

AN:

1459456

Hom.:

Cov.:

AF XY:

0.000344

AC XY:

250

AN XY:

726170

show subpopulations

Gnomad4 AFR exome

AF:

0.0131

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000360

Gnomad4 OTH exome

AF:

0.000878

GnomAD4 genome

AF:

0.00386

AC:

588

AN:

152288

Hom.:

Cov.:

AF XY:

0.00380

AC XY:

283

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0133

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00150

Hom.:

Bravo

AF:

0.00458

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2022	MYH9: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 02, 2018	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 30, 2012	Thr907Thr in Exon 22 of MYH9: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 1.8% (69/3738) of Afri can American chromosomes from a broad population by the NHLBI Exome Sequencing P roject (http://evs.gs.washington.edu/EVS; dbSNP rs148112044). -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Autosomal dominant nonsyndromic hearing loss 17

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.14

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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