rs1009150

Variant names:

• chr22-36306254-C-T
• rs1009150
• NM_002473.6:c.2037+160G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 17

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
• May-Hegglin anomaly

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
MYH9	NM_002473.6	c.2037+160G>A		intron_variant	Intron 16 of 40	ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.2037+160G>A		intron_variant	Intron 16 of 40	1	NM_002473.6	ENSP00000216181.6
MYH9	ENST00000685801.1	c.2100+160G>A		intron_variant	Intron 17 of 41			ENSP00000510688.1
MYH9	ENST00000687922.1	n.373+160G>A		intron_variant	Intron 2 of 2
MYH9	ENST00000691109.1	n.2332+160G>A		intron_variant	Intron 10 of 34

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

African (AFR) AF: 0.285 AC: 11781 AN: 41398

American (AMR) AF: 0.630 AC: 9625 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1843 AN: 3470

East Asian (EAS) AF: 0.275 AC: 1417 AN: 5146

South Asian (SAS) AF: 0.453 AC: 2175 AN: 4804

European-Finnish (FIN) AF: 0.699 AC: 7356 AN: 10518

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48072 AN: 67916

Other (OTH) AF: 0.572 AC: 1206 AN: 2110

Alfa AF: 0.654 Hom.: 42733

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

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.49
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1009150; hg19: chr22-36702300;