22-36332647-A-G

Variant names:

• chr22-36332647-A-G
• rs713659
• NM_002473.6:c.491-5159T>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.491-5159T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.50 (17934 hom., cov: 18)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH9	NM_002473.6	c.491-5159T>C		intron_variant	Intron 3 of 40	ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.491-5159T>C		intron_variant	Intron 3 of 40	1	NM_002473.6	ENSP00000216181.6

Frequencies

GnomAD3 genomes AF: 0.505 AC: 66205 AN: 131094 Hom.: 17937 Cov.: 18

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.505 AC: 66207 AN: 131166 Hom.: 17934 Cov.: 18 AF XY: 0.501 AC XY: 31174 AN XY: 62284

African (AFR) AF: 0.291 AC: 9455 AN: 32444

American (AMR) AF: 0.596 AC: 7445 AN: 12486

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1627 AN: 3360

East Asian (EAS) AF: 0.170 AC: 690 AN: 4058

South Asian (SAS) AF: 0.411 AC: 1587 AN: 3862

European-Finnish (FIN) AF: 0.621 AC: 4423 AN: 7124

Middle Eastern (MID) AF: 0.609 AC: 145 AN: 238

European-Non Finnish (NFE) AF: 0.606 AC: 39304 AN: 64906

Other (OTH) AF: 0.518 AC: 946 AN: 1826

Alfa AF: 0.547 Hom.: 2938

Bravo AF: 0.473

Asia WGS AF: 0.260 AC: 908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.85
PhyloP100		0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs713659; hg19: chr22-36728692;