rs182296792

chr22-36319502-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002473.6(MYH9):c.1108+38G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00285 in 1,595,088 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (11 hom.)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.27

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=-0.81).
• BP6: Variant 22-36319502-C-T is Benign according to our data. Variant chr22-36319502-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 258725.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00215 (327/152304) while in subpopulation NFE AF= 0.0031 (211/68026). AF 95% confidence interval is 0.00276. There are 0 homozygotes in gnomad4. There are 161 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 327 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6	c.1108+38G>A		intron_variant		ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.1108+38G>A		intron_variant		1	NM_002473.6	P1

Frequencies

GnomAD3 genomes AF: 0.00215 AC: 327 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000917

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00310

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00198 AC: 494 AN: 249712 Hom.: 3 AF XY: 0.00188 AC XY: 254 AN XY: 135058

Gnomad AFR exome AF: 0.000248

Gnomad AMR exome AF: 0.00375

Gnomad ASJ exome AF: 0.00329

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00126

Gnomad NFE exome AF: 0.00254

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00293 AC: 4222 AN: 1442784 Hom.: 11 Cov.: 28 AF XY: 0.00277 AC XY: 1991 AN XY: 718952

Gnomad4 AFR exome AF: 0.000726

Gnomad4 AMR exome AF: 0.00388

Gnomad4 ASJ exome AF: 0.00385

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.000806

Gnomad4 NFE exome AF: 0.00342

Gnomad4 OTH exome AF: 0.00219

GnomAD4 genome AF: 0.00215 AC: 327 AN: 152304 Hom.: 0 Cov.: 32 AF XY: 0.00216 AC XY: 161 AN XY: 74460

Gnomad4 AFR AF: 0.000914

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00310

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00226 Hom.: 0

Bravo AF: 0.00230

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	8.0
Dann	Benign	0.79

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: rs182296792; hg19: chr22-36715547;