Variant 22-36281868-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000216181.11(MYH9):c.*800T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.241 in 230,108 control chromosomes in the GnomAD database, including 7,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4507 hom., cov: 33)

Exomes 𝑓: 0.26 ( 2882 hom. )

Consequence

MYH9
ENST00000216181.11 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.41

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 22-36281868-A-G is Benign according to our data. Variant chr22-36281868-A-G is described in ClinVar as [Benign]. Clinvar id is 341469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 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.*800T>C		3_prime_UTR_variant	41/41	ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11 linkuse as main transcript	c.*800T>C		3_prime_UTR_variant	41/41	1	NM_002473.6	ENSP00000216181	P1	P35579-1

Frequencies

GnomAD3 genomes

AF:

0.233

AC:

35476

AN:

152104

Hom.:

4504

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.325

Gnomad EAS

AF:

0.0749

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.252

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.231

GnomAD4 exome

AF:

0.257

AC:

19978

AN:

77886

Hom.:

2882

Cov.:

AF XY:

0.258

AC XY:

9254

AN XY:

35910

show subpopulations

Gnomad4 AFR exome

AF:

0.149

Gnomad4 AMR exome

AF:

0.232

Gnomad4 ASJ exome

AF:

0.328

Gnomad4 EAS exome

AF:

0.0712

Gnomad4 SAS exome

AF:

0.191

Gnomad4 FIN exome

AF:

0.246

Gnomad4 NFE exome

AF:

0.300

Gnomad4 OTH exome

AF:

0.272

GnomAD4 genome

AF:

0.233

AC:

35487

AN:

152222

Hom.:

4507

Cov.:

AF XY:

0.229

AC XY:

17034

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.146

Gnomad4 AMR

AF:

0.229

Gnomad4 ASJ

AF:

0.325

Gnomad4 EAS

AF:

0.0747

Gnomad4 SAS

AF:

0.195

Gnomad4 FIN

AF:

0.252

Gnomad4 NFE

AF:

0.295

Gnomad4 OTH

AF:

0.228

Alfa

AF:

0.254

Hom.:

1987

Bravo

AF:

0.231

Asia WGS

AF:

0.118

AC:

413

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal dominant nonsyndromic hearing loss 17

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

MYH9-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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