rs2009930

Variant names:

• chr22-36303260-G-A
• rs2009930
• NM_002473.6:c.2391-584C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-36303260-G-A
• chr22-36303260-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002473.6(MYH9):​c.2391-584C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 151,610 control chromosomes in the GnomAD database, including 23,719 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (23719 hom., cov: 29)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH9	NM_002473.6	c.2391-584C>T		intron_variant	Intron 19 of 40	ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.2391-584C>T		intron_variant	Intron 19 of 40	1	NM_002473.6	ENSP00000216181.6
MYH9	ENST00000685801.1	c.2454-584C>T		intron_variant	Intron 20 of 41			ENSP00000510688.1
MYH9	ENST00000473022.1	n.32-584C>T		intron_variant	Intron 1 of 1	2
MYH9	ENST00000691109.1	n.2686-584C>T		intron_variant	Intron 13 of 34

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79211 AN: 151492 Hom.: 23723 Cov.: 29

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.522 AC: 79213 AN: 151610 Hom.: 23719 Cov.: 29 AF XY: 0.518 AC XY: 38361 AN XY: 74040

African (AFR) AF: 0.240 AC: 9892 AN: 41284

American (AMR) AF: 0.612 AC: 9334 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1793 AN: 3464

East Asian (EAS) AF: 0.224 AC: 1148 AN: 5130

South Asian (SAS) AF: 0.387 AC: 1863 AN: 4808

European-Finnish (FIN) AF: 0.656 AC: 6868 AN: 10462

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.682 AC: 46337 AN: 67910

Other (OTH) AF: 0.536 AC: 1128 AN: 2106

Alfa AF: 0.609 Hom.: 5945

Bravo AF: 0.508

Asia WGS AF: 0.254 AC: 885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.78
PhyloP100		-0.38
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: rs2009930; hg19: chr22-36699306;