chr22-36333029-A-G

Variant names:

• chr22-36333029-A-G
• rs4820234
• NM_002473.6:c.491-5541T>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.491-5541T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 151,982 control chromosomes in the GnomAD database, including 29,224 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 0.61 (29224 hom., cov: 31)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276
• Publications: 11 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: Labcorp Genetics (formerly Invitae), G2P
• macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
• 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 (AFR) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002473.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH9	NM_002473.6	MANE Select	c.491-5541T>C		intron	N/A	NP_002464.1	P35579-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH9	ENST00000216181.11	TSL:1 MANE Select	c.491-5541T>C		intron	N/A	ENSP00000216181.6	P35579-1
	MYH9	ENST00000401701.1	TSL:1	c.491-5541T>C		intron	N/A	ENSP00000384631.1	Q5BKV1
	MYH9	ENST00000685801.1		c.491-5541T>C		intron	N/A	ENSP00000510688.1	A0A8I5KWT8

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92651 AN: 151864 Hom.: 29196 Cov.: 31

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.610 AC: 92719 AN: 151982 Hom.: 29224 Cov.: 31 AF XY: 0.606 AC XY: 44989 AN XY: 74292

African (AFR) AF: 0.702 AC: 29092 AN: 41440

American (AMR) AF: 0.627 AC: 9574 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1672 AN: 3468

East Asian (EAS) AF: 0.161 AC: 836 AN: 5182

South Asian (SAS) AF: 0.397 AC: 1910 AN: 4808

European-Finnish (FIN) AF: 0.617 AC: 6519 AN: 10564

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41087 AN: 67944

Other (OTH) AF: 0.583 AC: 1225 AN: 2100

Alfa AF: 0.597 Hom.: 13915

Bravo AF: 0.617

Asia WGS AF: 0.294 AC: 1025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.27
PhyloP100		0.28
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: rs4820234; hg19: chr22-36729074;