rs3842715

chr22-36312004-CTCCTGTGA-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002473.6(MYH9):c.1728+37_1728+44del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,611,926 control chromosomes in the GnomAD database, including 50,136 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3998 hom., cov: 26)
  • Exomes 𝑓: 0.23 (46138 hom.)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.178

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 -16 ACMG points.

• BP6: Variant 22-36312004-CTCCTGTGA-C is Benign according to our data. Variant chr22-36312004-CTCCTGTGA-C is described in ClinVar as [Benign]. Clinvar id is 258730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6	c.1728+37_1728+44del		intron_variant		ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.1728+37_1728+44del		intron_variant		1	NM_002473.6	P1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30409 AN: 151968 Hom.: 3985 Cov.: 26

Gnomad AFR AF: 0.0820

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.230

GnomAD3 exomes AF: 0.272 AC: 68335 AN: 251072 Hom.: 11623 AF XY: 0.280 AC XY: 38077 AN XY: 135754

Gnomad AFR exome AF: 0.0767

Gnomad AMR exome AF: 0.291

Gnomad ASJ exome AF: 0.351

Gnomad EAS exome AF: 0.621

Gnomad SAS exome AF: 0.434

Gnomad FIN exome AF: 0.196

Gnomad NFE exome AF: 0.203

Gnomad OTH exome AF: 0.252

GnomAD4 exome AF: 0.232 AC: 338216 AN: 1459838 Hom.: 46138 AF XY: 0.238 AC XY: 172938 AN XY: 726222

Gnomad4 AFR exome AF: 0.0764

Gnomad4 AMR exome AF: 0.286

Gnomad4 ASJ exome AF: 0.353

Gnomad4 EAS exome AF: 0.623

Gnomad4 SAS exome AF: 0.430

Gnomad4 FIN exome AF: 0.195

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.257

GnomAD4 genome AF: 0.200 AC: 30445 AN: 152088 Hom.: 3998 Cov.: 26 AF XY: 0.208 AC XY: 15459 AN XY: 74326

Gnomad4 AFR AF: 0.0820

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.235

Alfa AF: 0.215 Hom.: 680

Bravo AF: 0.198

Asia WGS AF: 0.522 AC: 1814 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autosomal dominant nonsyndromic hearing loss 17 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3842715; hg19: chr22-36708049; COSMIC: COSV53381555; COSMIC: COSV53381555;