dbSNP rs2157256: MYH9:c.1728+433T>C (chr22-36311616-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002473.6(MYH9):c.1728+433T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,010 control chromosomes in the GnomAD database, including 24,648 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.55 ( 24648 hom., cov: 32)

Consequence

MYH9
NM_002473.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.61

Publications

18 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss 17
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
May-Hegglin anomaly
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MYH9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH9	NM_002473.6 link	c.1728+433T>C		intron_variant	Intron 14 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.1728+433T>C		intron_variant	Intron 14 of 40	1	NM_002473.6	ENSP00000216181.6		P35579-1

Frequencies

GnomAD3 genomes

AF:

0.546

AC:

82995

AN:

151892

Hom.:

24645

Cov.:

show subpopulations

Gnomad AFR

AF:

0.336

Gnomad AMI

AF:

0.761

Gnomad AMR

AF:

0.619

Gnomad ASJ

AF:

0.528

Gnomad EAS

AF:

0.222

Gnomad SAS

AF:

0.385

Gnomad FIN

AF:

0.651

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.676

Gnomad OTH

AF:

0.565

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.546

AC:

83021

AN:

152010

Hom.:

24648

Cov.:

AF XY:

0.541

AC XY:

40204

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.336

AC:

13915

AN:

41454

American (AMR)

AF:

0.618

AC:

9448

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.528

AC:

1831

AN:

3468

East Asian (EAS)

AF:

0.222

AC:

1147

AN:

5172

South Asian (SAS)

AF:

0.386

AC:

1856

AN:

4810

European-Finnish (FIN)

AF:

0.651

AC:

6867

AN:

10548

Middle Eastern (MID)

AF:

0.534

AC:

157

AN:

294

European-Non Finnish (NFE)

AF:

0.676

AC:

45928

AN:

67972

Other (OTH)

AF:

0.560

AC:

1178

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1733

3467

5200

6934

8667

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

692

1384

2076

2768

3460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.629

Hom.:

18166

Bravo

AF:

0.537

Asia WGS

AF:

0.260

AC:

905

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.19

(source)

DANN

Benign

0.27

PhyloP100

-2.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over