22-36281507-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002473.6(MYH9):c.*1160del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 194,486 control chromosomes in the GnomAD database, including 2,893 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2608 hom., cov: 29)
  • Exomes 𝑓: 0.29 (285 hom.)
• Consequence: MYH9 NM_002473.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.216

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 22-36281507-TA-T is Benign according to our data. Variant chr22-36281507-TA-T is described in ClinVar as [Benign]. Clinvar id is 341462.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6	c.*1160del		3_prime_UTR_variant	41/41	ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.*1160del		3_prime_UTR_variant	41/41	1	NM_002473.6	P1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 25336 AN: 147144 Hom.: 2604 Cov.: 29

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.000790

Gnomad SAS AF: 0.0416

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.295 AC: 13927 AN: 47278 Hom.: 285 Cov.: 0 AF XY: 0.296 AC XY: 6450 AN XY: 21786

Gnomad4 AFR exome AF: 0.386

Gnomad4 AMR exome AF: 0.276

Gnomad4 ASJ exome AF: 0.323

Gnomad4 EAS exome AF: 0.164

Gnomad4 SAS exome AF: 0.263

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.308

Gnomad4 OTH exome AF: 0.306

GnomAD4 genome AF: 0.172 AC: 25365 AN: 147208 Hom.: 2608 Cov.: 29 AF XY: 0.169 AC XY: 12100 AN XY: 71584

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.000792

Gnomad4 SAS AF: 0.0422

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.154

Bravo AF: 0.172

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Nonsyndromic Hearing Loss, Dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

MYH9-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs56058205; hg19: chr22-36677553;