rs8136069

Variant names:

• chr22-36326445-C-A
• rs8136069
• NM_002473.6:c.612+123G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-36326445-C-A
• chr22-36326445-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002473.6(MYH9):​c.612+123G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 948,970 control chromosomes in the GnomAD database, including 72,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9678 hom., cov: 33)
  • Exomes 𝑓: 0.38 (63022 hom.)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.866
• Publications: 14 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 22-36326445-C-A is Benign according to our data. Variant chr22-36326445-C-A is described in ClinVar as Benign. ClinVar VariationId is 1232746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH9	NM_002473.6	c.612+123G>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.612+123G>T		intron_variant	Intron 5 of 40	1	NM_002473.6	ENSP00000216181.6

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51558 AN: 152026 Hom.: 9655 Cov.: 33

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.361

GnomAD4 exome AF: 0.379 AC: 302033 AN: 796826 Hom.: 63022 AF XY: 0.387 AC XY: 163129 AN XY: 421794

African (AFR) AF: 0.245 AC: 5032 AN: 20546

American (AMR) AF: 0.341 AC: 14733 AN: 43164

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 9699 AN: 21962

East Asian (EAS) AF: 0.816 AC: 29900 AN: 36644

South Asian (SAS) AF: 0.526 AC: 38270 AN: 72794

European-Finnish (FIN) AF: 0.323 AC: 14153 AN: 43754

Middle Eastern (MID) AF: 0.327 AC: 1317 AN: 4024

European-Non Finnish (NFE) AF: 0.338 AC: 174090 AN: 515112

Other (OTH) AF: 0.382 AC: 14839 AN: 38826

GnomAD4 genome AF: 0.339 AC: 51613 AN: 152144 Hom.: 9678 Cov.: 33 AF XY: 0.345 AC XY: 25656 AN XY: 74380

African (AFR) AF: 0.246 AC: 10213 AN: 41510

American (AMR) AF: 0.333 AC: 5099 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1498 AN: 3470

East Asian (EAS) AF: 0.827 AC: 4281 AN: 5178

South Asian (SAS) AF: 0.560 AC: 2702 AN: 4826

European-Finnish (FIN) AF: 0.325 AC: 3435 AN: 10580

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23269 AN: 67976

Other (OTH) AF: 0.366 AC: 772 AN: 2108

Alfa AF: 0.347 Hom.: 29771

Bravo AF: 0.334

Asia WGS AF: 0.670 AC: 2328 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.84
PhyloP100		-0.87
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: rs8136069; hg19: chr22-36722490;