22-36282072-C-T

Variant summary

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

The NM_002473.6(MYH9):c.*596G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 236,098 control chromosomes in the GnomAD database, including 16,772 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 10100 hom., cov: 33)

Exomes 𝑓: 0.37 ( 6672 hom. )

Consequence

MYH9
NM_002473.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.502

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=-0.89).

BP6

Variant 22-36282072-C-T is Benign according to our data. Variant chr22-36282072-C-T is described in ClinVar as [Benign]. Clinvar id is 341475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6 linkuse as main transcript	c.*596G>A		3_prime_UTR_variant	41/41	ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11 linkuse as main transcript	c.*596G>A		3_prime_UTR_variant	41/41	1	NM_002473.6	P1	P35579-1

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49539

AN:

152012

Hom.:

10100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0897

Gnomad AMI

AF:

0.625

Gnomad AMR

AF:

0.423

Gnomad ASJ

AF:

0.375

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.403

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.452

Gnomad OTH

AF:

0.351

GnomAD4 exome

AF:

0.374

AC:

31392

AN:

83968

Hom.:

6672

Cov.:

AF XY:

0.376

AC XY:

14634

AN XY:

38914

show subpopulations

Gnomad4 AFR exome

AF:

0.0814

Gnomad4 AMR exome

AF:

0.414

Gnomad4 ASJ exome

AF:

0.373

Gnomad4 EAS exome

AF:

0.129

Gnomad4 SAS exome

AF:

0.214

Gnomad4 FIN exome

AF:

0.419

Gnomad4 NFE exome

AF:

0.450

Gnomad4 OTH exome

AF:

0.374

GnomAD4 genome

AF:

0.326

AC:

49534

AN:

152130

Hom.:

10100

Cov.:

AF XY:

0.323

AC XY:

24005

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0894

Gnomad4 AMR

AF:

0.423

Gnomad4 ASJ

AF:

0.375

Gnomad4 EAS

AF:

0.126

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.403

Gnomad4 NFE

AF:

0.452

Gnomad4 OTH

AF:

0.348

Alfa

AF:

0.394

Hom.:

3160

Bravo

AF:

0.319

Asia WGS

AF:

0.151

AC:

525

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

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

-0.89

Cadd

Benign

0.44

Dann

Benign

0.39

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