rs2157257

chr22-36312293-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002473.6(MYH9):c.1555-71T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 1,537,632 control chromosomes in the GnomAD database, including 309,404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (23360 hom., cov: 31)
  • Exomes 𝑓: 0.63 (286044 hom.)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.344

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 22-36312293-A-G is Benign according to our data. Variant chr22-36312293-A-G is described in ClinVar as [Benign]. Clinvar id is 1243503.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6	c.1555-71T>C		intron_variant		ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.1555-71T>C		intron_variant		1	NM_002473.6	P1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78682 AN: 151896 Hom.: 23364 Cov.: 31

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.541

GnomAD4 exome AF: 0.631 AC: 874468 AN: 1385618 Hom.: 286044 AF XY: 0.626 AC XY: 432093 AN XY: 690724

Gnomad4 AFR exome AF: 0.224

Gnomad4 AMR exome AF: 0.630

Gnomad4 ASJ exome AF: 0.520

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.415

Gnomad4 FIN exome AF: 0.660

Gnomad4 NFE exome AF: 0.680

Gnomad4 OTH exome AF: 0.583

GnomAD4 genome AF: 0.518 AC: 78685 AN: 152014 Hom.: 23360 Cov.: 31 AF XY: 0.514 AC XY: 38164 AN XY: 74292

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.652

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.536

Alfa AF: 0.611 Hom.: 4610

Bravo AF: 0.504

Asia WGS AF: 0.253 AC: 881 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.8
Dann	Benign	0.73

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: rs2157257; hg19: chr22-36708338; COSMIC: COSV53395916; COSMIC: COSV53395916;