rs8136336

Variant names:

• chr22-36326489-G-A
• rs8136336
• NM_002473.6:c.612+79C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-36326489-G-A
• chr22-36326489-G-C
• chr22-36326489-G-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+79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 1,277,416 control chromosomes in the GnomAD database, including 622,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (73742 hom., cov: 34)
  • Exomes 𝑓: 0.99 (548917 hom.)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.525
• Publications: 8 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=-0.89).
• BP6: Variant 22-36326489-G-A is Benign according to our data. Variant chr22-36326489-G-A is described in ClinVar as Benign. ClinVar VariationId is 1291297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH9	NM_002473.6	c.612+79C>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+79C>T		intron_variant	Intron 5 of 40	1	NM_002473.6	ENSP00000216181.6

Frequencies

GnomAD3 genomes AF: 0.984 AC: 149779 AN: 152254 Hom.: 73683 Cov.: 34

Gnomad AFR AF: 0.971

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.987

Gnomad ASJ AF: 0.973

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.991

Gnomad FIN AF: 0.998

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.987

Gnomad OTH AF: 0.983

GnomAD4 exome AF: 0.988 AC: 1111304 AN: 1125044 Hom.: 548917 AF XY: 0.988 AC XY: 568618 AN XY: 575612

African (AFR) AF: 0.971 AC: 25969 AN: 26738

American (AMR) AF: 0.992 AC: 43884 AN: 44244

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 23399 AN: 24006

East Asian (EAS) AF: 1.00 AC: 38203 AN: 38214

South Asian (SAS) AF: 0.992 AC: 78977 AN: 79650

European-Finnish (FIN) AF: 0.997 AC: 52204 AN: 52342

Middle Eastern (MID) AF: 0.958 AC: 4936 AN: 5154

European-Non Finnish (NFE) AF: 0.987 AC: 795052 AN: 805312

Other (OTH) AF: 0.986 AC: 48680 AN: 49384

GnomAD4 genome AF: 0.984 AC: 149897 AN: 152372 Hom.: 73742 Cov.: 34 AF XY: 0.984 AC XY: 73334 AN XY: 74514

African (AFR) AF: 0.971 AC: 40375 AN: 41592

American (AMR) AF: 0.988 AC: 15117 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.973 AC: 3377 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5185 AN: 5186

South Asian (SAS) AF: 0.991 AC: 4782 AN: 4826

European-Finnish (FIN) AF: 0.998 AC: 10609 AN: 10626

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.987 AC: 67183 AN: 68042

Other (OTH) AF: 0.983 AC: 2079 AN: 2114

Alfa AF: 0.984 Hom.: 19436

Bravo AF: 0.983

Asia WGS AF: 0.992 AC: 3449 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 90% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 84. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.34
DANN	Benign	0.65
PhyloP100		-0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs8136336; hg19: chr22-36722534;