22-36281507-TA-T

Variant names:

• chr22-36281507-TA-T
• rs56058205
• NM_002473.6:c.*1160delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002473.6(MYH9):​c.*1160delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 194,486 control chromosomes in the GnomAD database, including 2,893 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2608 hom., cov: 29)
  • Exomes 𝑓: 0.29 (285 hom.)
• Consequence: MYH9 NM_002473.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.216
• 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 -10 ACMG points.

• BP6: Variant 22-36281507-TA-T is Benign according to our data. Variant chr22-36281507-TA-T is described in ClinVar as [Benign]. Clinvar id is 341462.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH9	NM_002473.6	c.*1160delT		3_prime_UTR_variant	Exon 41 of 41	ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.*1160delT		3_prime_UTR_variant	Exon 41 of 41	1	NM_002473.6	ENSP00000216181.6

Frequencies

GnomAD3 genomes AF: 0.172 AC: 25336 AN: 147144 Hom.: 2604 Cov.: 29

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.000790

Gnomad SAS AF: 0.0416

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.295 AC: 13927 AN: 47278 Hom.: 285 Cov.: 0 AF XY: 0.296 AC XY: 6450 AN XY: 21786

African (AFR) AF: 0.386 AC: 1028 AN: 2664

American (AMR) AF: 0.276 AC: 410 AN: 1486

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 976 AN: 3022

East Asian (EAS) AF: 0.164 AC: 878 AN: 5338

South Asian (SAS) AF: 0.263 AC: 93 AN: 354

European-Finnish (FIN) AF: 0.173 AC: 59 AN: 342

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 9148 AN: 29682

Other (OTH) AF: 0.306 AC: 1255 AN: 4096

GnomAD4 genome AF: 0.172 AC: 25365 AN: 147208 Hom.: 2608 Cov.: 29 AF XY: 0.169 AC XY: 12100 AN XY: 71584

African (AFR) AF: 0.292 AC: 11853 AN: 40656

American (AMR) AF: 0.106 AC: 1563 AN: 14762

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 528 AN: 3408

East Asian (EAS) AF: 0.000792 AC: 4 AN: 5050

South Asian (SAS) AF: 0.0422 AC: 197 AN: 4670

European-Finnish (FIN) AF: 0.141 AC: 1299 AN: 9212

Middle Eastern (MID) AF: 0.106 AC: 30 AN: 282

European-Non Finnish (NFE) AF: 0.142 AC: 9394 AN: 66268

Other (OTH) AF: 0.154 AC: 310 AN: 2008

Alfa AF: 0.0572 Hom.: 65

Bravo AF: 0.172

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Nonsyndromic Hearing Loss, Dominant Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

MYH9-related disorder Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.22
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: rs56058205; hg19: chr22-36677553;