rs12159211

Variant names:

• chr22-36323118-G-A
• rs12159211
• NM_002473.6:c.613-597C>T

Variant summary

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

The NM_002473.6(MYH9):​c.613-597C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 152,282 control chromosomes in the GnomAD database, including 165 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 0.042 (165 hom., cov: 33)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.054 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH9	NM_002473.6	c.613-597C>T		intron_variant	Intron 5 of 40	ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.613-597C>T		intron_variant	Intron 5 of 40	1	NM_002473.6	ENSP00000216181.6

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 6399 AN: 152164 Hom.: 166 Cov.: 33

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0342

Gnomad ASJ AF: 0.0691

Gnomad EAS AF: 0.0144

Gnomad SAS AF: 0.0602

Gnomad FIN AF: 0.0650

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0484

Gnomad OTH AF: 0.0474

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

GnomAD4 genome AF: 0.0420 AC: 6396 AN: 152282 Hom.: 165 Cov.: 33 AF XY: 0.0418 AC XY: 3110 AN XY: 74462

African (AFR) AF: 0.0277 AC: 1149 AN: 41534

American (AMR) AF: 0.0341 AC: 522 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0691 AC: 240 AN: 3472

East Asian (EAS) AF: 0.0145 AC: 75 AN: 5180

South Asian (SAS) AF: 0.0596 AC: 288 AN: 4830

European-Finnish (FIN) AF: 0.0650 AC: 690 AN: 10616

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0484 AC: 3290 AN: 68028

Other (OTH) AF: 0.0473 AC: 100 AN: 2112

Alfa AF: 0.0431 Hom.: 57

Bravo AF: 0.0393

Asia WGS AF: 0.0430 AC: 148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.057
DANN	Benign	0.68
PhyloP100		-1.1
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: rs12159211; hg19: chr22-36719163;