rs6000239

chr22-36319984-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
MYH9	NM_002473.6	c.1012+236A>G		intron_variant		ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.1012+236A>G		intron_variant		1	NM_002473.6	P1

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

Gnomad4 AFR exome AF: 0.645

Gnomad4 AMR exome AF: 0.645

Gnomad4 ASJ exome AF: 0.533

Gnomad4 EAS exome AF: 0.185

Gnomad4 SAS exome AF: 0.461

Gnomad4 FIN exome AF: 0.676

Gnomad4 NFE exome AF: 0.648

Gnomad4 OTH exome AF: 0.596

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

Gnomad4 AFR AF: 0.647

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.598

Alfa AF: 0.619 Hom.: 12390

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.1
Dann	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs6000239; hg19: chr22-36716029;