rs372865551

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002473.6(MYH9):c.1843+14C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,610,208 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 0.00070 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

MYH9
NM_002473.6 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.61

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 22-36309268-G-T is Benign according to our data. Variant chr22-36309268-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 164455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36309268-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 164455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36309268-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 164455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36309268-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 164455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36309268-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 164455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36309268-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 164455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36309268-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 164455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36309268-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 164455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36309268-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 164455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36309268-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 164455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36309268-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 164455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36309268-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 164455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36309268-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 164455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36309268-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 164455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36309268-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 164455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36309268-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 164455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36309268-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 164455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36309268-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 164455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36309268-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 164455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36309268-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 164455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000702 (107/152336) while in subpopulation AFR AF = 0.00238 (99/41572). AF 95% confidence interval is 0.002. There are 0 homozygotes in GnomAd4. There are 51 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 107 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH9	NM_002473.6 link	c.1843+14C>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+14C>A		intron_variant	Intron 15 of 40	1	NM_002473.6	ENSP00000216181.6		P35579-1

Frequencies

GnomAD3 genomes

AF:

0.000703

AC:

107

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00239

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000132

AC:

AN:

250892

AF XY:

0.000118

show subpopulations

Gnomad AFR exome

AF:

0.00179

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000631

AC:

AN:

1457872

Hom.:

Cov.:

AF XY:

0.0000593

AC XY:

AN XY:

725590

show subpopulations

African (AFR)

AF:

0.00204

AC:

AN:

33392

American (AMR)

AF:

0.000134

AC:

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

86136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000722

AC:

AN:

1108406

Other (OTH)

AF:

0.000166

AC:

AN:

60288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

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:

0.000702

AC:

107

AN:

152336

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00238

AC:

AN:

41572

American (AMR)

AF:

0.000523

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.000391

Hom.:

Bravo

AF:

0.000808

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 13, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

1843+14C>A in Intron 15 of MYH9: This variant is not expected to have clinical s ignificance because it is not located within the conserved splice consensus sequ ence and has been identified in 0.1% (4/4406) of African American chromosomes fr om a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washi ngton.edu/EVS). -

Autosomal dominant nonsyndromic hearing loss 17;C5200934:Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss

Benign:1

Dec 09, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.80

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

2.6

Mutation Taster

=100/0

polymorphism

(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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over