Genetic Variant MYH9:c.1843+287G>A (chr22-36308995-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002473.6(MYH9):c.1843+287G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 427,364 control chromosomes in the GnomAD database, including 10,300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.20 ( 3977 hom., cov: 33)

Exomes 𝑓: 0.20 ( 6323 hom. )

Consequence

MYH9
NM_002473.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.585

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 22-36308995-C-T is Benign according to our data. Variant chr22-36308995-C-T is described in ClinVar as [Benign]. Clinvar id is 1276781.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH9	NM_002473.6 link	c.1843+287G>A		intron_variant	Intron 15 of 40	ENST00000216181.11	NP_002464.1	P35579-1A0A024R1N1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11 link	c.1843+287G>A		intron_variant	Intron 15 of 40	1	NM_002473.6	ENSP00000216181.6		P35579-1

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29698

AN:

152012

Hom.:

3963

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0654

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.252

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.625

Gnomad SAS

AF:

0.446

Gnomad FIN

AF:

0.194

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.203

Gnomad OTH

AF:

0.223

GnomAD4 exome

AF:

0.199

AC:

54800

AN:

275234

Hom.:

6323

AF XY:

0.200

AC XY:

26174

AN XY:

130574

show subpopulations

Gnomad4 AFR exome

AF:

0.0440

Gnomad4 AMR exome

AF:

0.227

Gnomad4 ASJ exome

AF:

0.345

Gnomad4 EAS exome

AF:

0.612

Gnomad4 SAS exome

AF:

0.416

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.193

Gnomad4 OTH exome

AF:

0.244

GnomAD4 genome

AF:

0.195

AC:

29734

AN:

152130

Hom.:

3977

Cov.:

AF XY:

0.203

AC XY:

15131

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0654

Gnomad4 AMR

AF:

0.252

Gnomad4 ASJ

AF:

0.351

Gnomad4 EAS

AF:

0.627

Gnomad4 SAS

AF:

0.445

Gnomad4 FIN

AF:

0.194

Gnomad4 NFE

AF:

0.203

Gnomad4 OTH

AF:

0.229

Alfa

AF:

0.213

Hom.:

4173

Bravo

AF:

0.193

Asia WGS

AF:

0.529

AC:

1837

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.3

DANN

Benign

0.84

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