rs2157257

Positions:

• chr22-36312293-A-G

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.1555-71T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 1,537,632 control chromosomes in the GnomAD database, including 309,404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (23360 hom., cov: 31)
  • Exomes 𝑓: 0.63 (286044 hom.)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.344

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=-0.83).
• BP6: Variant 22-36312293-A-G is Benign according to our data. Variant chr22-36312293-A-G is described in ClinVar as [Benign]. Clinvar id is 1243503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH9	NM_002473.6	c.1555-71T>C		intron_variant		ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.1555-71T>C		intron_variant		1	NM_002473.6	ENSP00000216181	P1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78682 AN: 151896 Hom.: 23364 Cov.: 31

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.541

GnomAD4 exome AF: 0.631 AC: 874468 AN: 1385618 Hom.: 286044 AF XY: 0.626 AC XY: 432093 AN XY: 690724

Gnomad4 AFR exome AF: 0.224

Gnomad4 AMR exome AF: 0.630

Gnomad4 ASJ exome AF: 0.520

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.415

Gnomad4 FIN exome AF: 0.660

Gnomad4 NFE exome AF: 0.680

Gnomad4 OTH exome AF: 0.583

GnomAD4 genome AF: 0.518 AC: 78685 AN: 152014 Hom.: 23360 Cov.: 31 AF XY: 0.514 AC XY: 38164 AN XY: 74292

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.652

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.536

Alfa AF: 0.611 Hom.: 4610

Bravo AF: 0.504

Asia WGS AF: 0.253 AC: 881 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 24, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 89% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 83. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.8
DANN	Benign	0.73

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: rs2157257; hg19: chr22-36708338; COSMIC: COSV53395916; COSMIC: COSV53395916;