rs1009150

Positions:

• chr22-36306254-C-T

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.2037+160G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 151,846 control chromosomes in the GnomAD database, including 26,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.56 (26168 hom., cov: 30)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.322

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=-0.82).
• BP6: Variant 22-36306254-C-T is Benign according to our data. Variant chr22-36306254-C-T is described in ClinVar as [Benign]. Clinvar id is 1280377.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6	c.2037+160G>A		intron_variant		ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.2037+160G>A		intron_variant		1	NM_002473.6	P1
MYH9	ENST00000685801.1	c.2100+160G>A		intron_variant
MYH9	ENST00000687922.1	n.373+160G>A		intron_variant, non_coding_transcript_variant
MYH9	ENST00000691109.1	n.2332+160G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84328 AN: 151728 Hom.: 26170 Cov.: 30

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.577

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.555 AC: 84340 AN: 151846 Hom.: 26168 Cov.: 30 AF XY: 0.552 AC XY: 40935 AN XY: 74166

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.699

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.572

Alfa AF: 0.670 Hom.: 34015

Bravo AF: 0.540

Asia WGS AF: 0.322 AC: 1122 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 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.49

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: rs1009150; hg19: chr22-36702300;