rs56020676

chr22-36294074-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002473.6(MYH9):c.3837+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0263 in 1,605,878 control chromosomes in the GnomAD database, including 3,285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.087 (1599 hom., cov: 33)
  • Exomes 𝑓: 0.020 (1686 hom.)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.775

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 22-36294074-T-C is Benign according to our data. Variant chr22-36294074-T-C is described in ClinVar as [Benign]. Clinvar id is 258744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6	c.3837+18A>G		intron_variant		ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.3837+18A>G		intron_variant		1	NM_002473.6	P1
MYH9	ENST00000685801.1	c.3900+18A>G		intron_variant
MYH9	ENST00000691109.1	n.4132+18A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0873 AC: 13281 AN: 152062 Hom.: 1596 Cov.: 33

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0395

Gnomad ASJ AF: 0.0211

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00870

Gnomad FIN AF: 0.0184

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.0589

GnomAD3 exomes AF: 0.0312 AC: 7610 AN: 244238 Hom.: 683 AF XY: 0.0259 AC XY: 3443 AN XY: 132756

Gnomad AFR exome AF: 0.279

Gnomad AMR exome AF: 0.0217

Gnomad ASJ exome AF: 0.0201

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.00889

Gnomad FIN exome AF: 0.0186

Gnomad NFE exome AF: 0.0128

Gnomad OTH exome AF: 0.0290

GnomAD4 exome AF: 0.0199 AC: 28996 AN: 1453698 Hom.: 1686 Cov.: 36 AF XY: 0.0188 AC XY: 13616 AN XY: 723634

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.0224

Gnomad4 ASJ exome AF: 0.0193

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00954

Gnomad4 FIN exome AF: 0.0189

Gnomad4 NFE exome AF: 0.0125

Gnomad4 OTH exome AF: 0.0284

GnomAD4 genome AF: 0.0874 AC: 13294 AN: 152180 Hom.: 1599 Cov.: 33 AF XY: 0.0848 AC XY: 6309 AN XY: 74412

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.0396

Gnomad4 ASJ AF: 0.0211

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00850

Gnomad4 FIN AF: 0.0184

Gnomad4 NFE AF: 0.0130

Gnomad4 OTH AF: 0.0582

Alfa AF: 0.0483 Hom.: 130

Bravo AF: 0.0970

Asia WGS AF: 0.0190 AC: 69 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 13, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.89
Dann	Benign	0.52

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: rs56020676; hg19: chr22-36690120;