chr22-36288239-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002473.6(MYH9):c.4932+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,613,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

MYH9
NM_002473.6 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.48

Publications

0 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 22-36288239-C-T is Benign according to our data. Variant chr22-36288239-C-T is described in CliVar as Likely_benign. Clinvar id is 178430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36288239-C-T is described in CliVar as Likely_benign. Clinvar id is 178430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36288239-C-T is described in CliVar as Likely_benign. Clinvar id is 178430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36288239-C-T is described in CliVar as Likely_benign. Clinvar id is 178430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36288239-C-T is described in CliVar as Likely_benign. Clinvar id is 178430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36288239-C-T is described in CliVar as Likely_benign. Clinvar id is 178430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36288239-C-T is described in CliVar as Likely_benign. Clinvar id is 178430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36288239-C-T is described in CliVar as Likely_benign. Clinvar id is 178430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36288239-C-T is described in CliVar as Likely_benign. Clinvar id is 178430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36288239-C-T is described in CliVar as Likely_benign. Clinvar id is 178430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36288239-C-T is described in CliVar as Likely_benign. Clinvar id is 178430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36288239-C-T is described in CliVar as Likely_benign. Clinvar id is 178430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36288239-C-T is described in CliVar as Likely_benign. Clinvar id is 178430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36288239-C-T is described in CliVar as Likely_benign. Clinvar id is 178430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36288239-C-T is described in CliVar as Likely_benign. Clinvar id is 178430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36288239-C-T is described in CliVar as Likely_benign. Clinvar id is 178430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36288239-C-T is described in CliVar as Likely_benign. Clinvar id is 178430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36288239-C-T is described in CliVar as Likely_benign. Clinvar id is 178430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36288239-C-T is described in CliVar as Likely_benign. Clinvar id is 178430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36288239-C-T is described in CliVar as Likely_benign. Clinvar id is 178430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAdExome4 at 35 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH9	NM_002473.6 link	c.4932+13G>A		intron_variant	Intron 34 of 40	ENST00000216181.11	NP_002464.1	P35579-1A0A024R1N1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYH9	ENST00000216181.11 link	c.4932+13G>A	intron_variant	Intron 34 of 40	1	NM_002473.6	ENSP00000216181.6	P35579-1
MYH9	ENST00000685801.1 link	c.4995+13G>A	intron_variant	Intron 35 of 41			ENSP00000510688.1	A0A8I5KWT8
MYH9	ENST00000691109.1 link	n.5227+13G>A	intron_variant	Intron 28 of 34
MYH9	ENST00000685708.1 link	n.-28G>A	upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000160

AC:

AN:

250606

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000240

AC:

AN:

1461150

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

726902

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33478

American (AMR)

AF:

0.0000447

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52798

Middle Eastern (MID)

AF:

0.000348

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000207

AC:

AN:

1111936

Other (OTH)

AF:

0.0000663

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41560

American (AMR)

AF:

0.0000654

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000302

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 30, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

c.4932+13G>A in Intron 34 of MYH9: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus se quence and has been identified in 1/7020 European American chromosomes from a br oad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.e du/EVS). -

not provided

Benign:1

Jun 03, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.63

CADD

Benign

0.037

(source)

DANN

Benign

0.95

PhyloP100

-2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over