rs5995288

Variant names:

• chr22-36366589-T-C
• rs5995288
• NM_002473.6:c.-19-17334A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-36366589-T-C
• chr22-36366589-T-G

Variant summary

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

The NM_002473.6(MYH9):​c.-19-17334A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,906 control chromosomes in the GnomAD database, including 29,637 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 0.62 (29637 hom., cov: 30)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH9	NM_002473.6	c.-19-17334A>G		intron_variant	Intron 1 of 40	ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.-19-17334A>G		intron_variant	Intron 1 of 40	1	NM_002473.6	ENSP00000216181.6

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93557 AN: 151790 Hom.: 29605 Cov.: 30

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.616 AC: 93640 AN: 151906 Hom.: 29637 Cov.: 30 AF XY: 0.607 AC XY: 45074 AN XY: 74258

African (AFR) AF: 0.578 AC: 23930 AN: 41366

American (AMR) AF: 0.642 AC: 9804 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2074 AN: 3470

East Asian (EAS) AF: 0.165 AC: 855 AN: 5172

South Asian (SAS) AF: 0.381 AC: 1835 AN: 4816

European-Finnish (FIN) AF: 0.613 AC: 6477 AN: 10566

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.683 AC: 46431 AN: 67936

Other (OTH) AF: 0.624 AC: 1311 AN: 2102

Alfa AF: 0.653 Hom.: 4233

Bravo AF: 0.619

Asia WGS AF: 0.320 AC: 1111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.47
PhyloP100		-1.5
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: rs5995288; hg19: chr22-36762634;