Variant rs2157257 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.344

Variant links:

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]

MYH9 links:

MYH9 (HGNC:):

MYH9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.1555-71T>C		intron_variant		ENST00000216181.11	NP_002464.1	P35579-1A0A024R1N1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11 linkuse as main transcript	c.1555-71T>C		intron_variant		1	NM_002473.6	ENSP00000216181.6		P35579-1

Frequencies

GnomAD3 genomes

AF:

0.518

AC:

78682

AN:

151896

Hom.:

23364

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.514

AC XY:

38164

AN XY:

74292

show subpopulations

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 24, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over