rs6000233

Positions:

• chr22-36291916-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.4344+70A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0316 in 1,609,530 control chromosomes in the GnomAD database, including 5,561 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (2798 hom., cov: 33)
  • Exomes 𝑓: 0.023 (2763 hom.)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.53

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=-0.93).
• BP6: Variant 22-36291916-T-C is Benign according to our data. Variant chr22-36291916-T-C is described in ClinVar as [Benign]. Clinvar id is 1286826.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6	c.4344+70A>G		intron_variant		ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.4344+70A>G		intron_variant		1	NM_002473.6	P1
MYH9	ENST00000685801.1	c.4407+70A>G		intron_variant
MYH9	ENST00000691109.1	n.4639+70A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17296 AN: 152096 Hom.: 2784 Cov.: 33

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0563

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.0184

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0136

Gnomad OTH AF: 0.0884

GnomAD4 exome AF: 0.0230 AC: 33530 AN: 1457316 Hom.: 2763 AF XY: 0.0215 AC XY: 15581 AN XY: 725104

Gnomad4 AFR exome AF: 0.379

Gnomad4 AMR exome AF: 0.0315

Gnomad4 ASJ exome AF: 0.0193

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0105

Gnomad4 FIN exome AF: 0.0187

Gnomad4 NFE exome AF: 0.0129

Gnomad4 OTH exome AF: 0.0393

GnomAD4 genome AF: 0.114 AC: 17356 AN: 152214 Hom.: 2798 Cov.: 33 AF XY: 0.111 AC XY: 8258 AN XY: 74414

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.0563

Gnomad4 ASJ AF: 0.0210

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00911

Gnomad4 FIN AF: 0.0184

Gnomad4 NFE AF: 0.0136

Gnomad4 OTH AF: 0.0875

Alfa AF: 0.0578 Hom.: 267

Bravo AF: 0.129

Asia WGS AF: 0.0330 AC: 115 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.029
DANN	Benign	0.30

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: rs6000233; hg19: chr22-36687962;