chr22-36321743-G-C

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.769+15C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000294 in 1,460,560 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: not found (cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

MYH9
NM_002473.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.31

Publications

1 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=-0.88).

BP6

Variant 22-36321743-G-C is Benign according to our data. Variant chr22-36321743-G-C is described in CliVar as Likely_benign. Clinvar id is 258766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36321743-G-C is described in CliVar as Likely_benign. Clinvar id is 258766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36321743-G-C is described in CliVar as Likely_benign. Clinvar id is 258766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36321743-G-C is described in CliVar as Likely_benign. Clinvar id is 258766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36321743-G-C is described in CliVar as Likely_benign. Clinvar id is 258766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36321743-G-C is described in CliVar as Likely_benign. Clinvar id is 258766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36321743-G-C is described in CliVar as Likely_benign. Clinvar id is 258766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36321743-G-C is described in CliVar as Likely_benign. Clinvar id is 258766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36321743-G-C is described in CliVar as Likely_benign. Clinvar id is 258766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36321743-G-C is described in CliVar as Likely_benign. Clinvar id is 258766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36321743-G-C is described in CliVar as Likely_benign. Clinvar id is 258766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36321743-G-C is described in CliVar as Likely_benign. Clinvar id is 258766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36321743-G-C is described in CliVar as Likely_benign. Clinvar id is 258766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36321743-G-C is described in CliVar as Likely_benign. Clinvar id is 258766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36321743-G-C is described in CliVar as Likely_benign. Clinvar id is 258766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36321743-G-C is described in CliVar as Likely_benign. Clinvar id is 258766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36321743-G-C is described in CliVar as Likely_benign. Clinvar id is 258766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36321743-G-C is described in CliVar as Likely_benign. Clinvar id is 258766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36321743-G-C is described in CliVar as Likely_benign. Clinvar id is 258766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36321743-G-C is described in CliVar as Likely_benign. Clinvar id is 258766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAdExome4 at 43 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH9	NM_002473.6 link	c.769+15C>G		intron_variant	Intron 7 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.769+15C>G		intron_variant	Intron 7 of 40	1	NM_002473.6	ENSP00000216181.6		P35579-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000795

AC:

AN:

251488

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1460560

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

726686

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33450

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86218

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000360

AC:

AN:

1110844

Other (OTH)

AF:

0.0000331

AC:

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Nov 06, 2023

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

-0.88

CADD

Benign

0.034

(source)

DANN

Benign

0.67

PhyloP100

-3.3

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over