rs6000239

Variant names:

• chr22-36319984-T-C
• rs6000239
• NM_002473.6:c.1012+236A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002473.6(MYH9):​c.1012+236A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 627,824 control chromosomes in the GnomAD database, including 118,339 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (30163 hom., cov: 32)
  • Exomes 𝑓: 0.59 (88176 hom.)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.991
• Publications: 7 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 22-36319984-T-C is Benign according to our data. Variant chr22-36319984-T-C is described in ClinVar as Benign. ClinVar VariationId is 1239250.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH9	NM_002473.6	c.1012+236A>G		intron_variant	Intron 9 of 40	ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.1012+236A>G		intron_variant	Intron 9 of 40	1	NM_002473.6	ENSP00000216181.6

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94561 AN: 151916 Hom.: 30153 Cov.: 32

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.603

GnomAD4 exome AF: 0.594 AC: 282799 AN: 475788 Hom.: 88176 AF XY: 0.587 AC XY: 147270 AN XY: 251082

African (AFR) AF: 0.645 AC: 8447 AN: 13094

American (AMR) AF: 0.645 AC: 13127 AN: 20356

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 7452 AN: 13976

East Asian (EAS) AF: 0.185 AC: 5747 AN: 31070

South Asian (SAS) AF: 0.461 AC: 21832 AN: 47318

European-Finnish (FIN) AF: 0.676 AC: 19613 AN: 29008

Middle Eastern (MID) AF: 0.613 AC: 1244 AN: 2028

European-Non Finnish (NFE) AF: 0.648 AC: 189359 AN: 292126

Other (OTH) AF: 0.596 AC: 15978 AN: 26812

GnomAD4 genome AF: 0.622 AC: 94596 AN: 152036 Hom.: 30163 Cov.: 32 AF XY: 0.617 AC XY: 45883 AN XY: 74320

African (AFR) AF: 0.647 AC: 26816 AN: 41462

American (AMR) AF: 0.641 AC: 9791 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1864 AN: 3464

East Asian (EAS) AF: 0.170 AC: 877 AN: 5158

South Asian (SAS) AF: 0.429 AC: 2070 AN: 4820

European-Finnish (FIN) AF: 0.674 AC: 7120 AN: 10558

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.647 AC: 43956 AN: 67980

Other (OTH) AF: 0.598 AC: 1259 AN: 2106

Alfa AF: 0.618 Hom.: 14056

Bravo AF: 0.622

Asia WGS AF: 0.311 AC: 1085 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 29, 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	-0.91
CADD	Benign	1.1
DANN	Benign	0.70
PhyloP100		-0.99
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: rs6000239; hg19: chr22-36716029;