rs76330062

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.2159+39C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0424 in 1,611,282 control chromosomes in the GnomAD database, including 1,682 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 117 hom., cov: 33)

Exomes 𝑓: 0.043 ( 1565 hom. )

Consequence

MYH9
NM_002473.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.65

Publications

3 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: Labcorp Genetics (formerly Invitae), G2P
macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
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=-0.83).

BP6

Variant 22-36305891-G-T is Benign according to our data. Variant chr22-36305891-G-T is described in ClinVar as Benign. ClinVar VariationId is 258733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0328 (5002/152296) while in subpopulation NFE AF = 0.0493 (3356/68008). AF 95% confidence interval is 0.048. There are 117 homozygotes in GnomAd4. There are 2344 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 5002 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002473.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH9	NM_002473.6	MANE Select	c.2159+39C>A		intron	N/A	NP_002464.1	P35579-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYH9	ENST00000216181.11	TSL:1 MANE Select	c.2159+39C>A	intron	N/A	ENSP00000216181.6	P35579-1
MYH9	ENST00000685801.1		c.2222+39C>A	intron	N/A	ENSP00000510688.1	A0A8I5KWT8
MYH9	ENST00000955568.1		c.2222+39C>A	intron	N/A	ENSP00000625627.1

Frequencies

GnomAD3 genomes

AF:

0.0329

AC:

5000

AN:

152178

Hom.:

117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0102

Gnomad AMI

AF:

0.0637

Gnomad AMR

AF:

0.0405

Gnomad ASJ

AF:

0.0530

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00746

Gnomad FIN

AF:

0.0228

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0493

Gnomad OTH

AF:

0.0339

GnomAD2 exomes

AF:

0.0345

AC:

8589

AN:

249288

AF XY:

0.0350

show subpopulations

Gnomad AFR exome

AF:

0.00938

Gnomad AMR exome

AF:

0.0289

Gnomad ASJ exome

AF:

0.0582

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0231

Gnomad NFE exome

AF:

0.0517

Gnomad OTH exome

AF:

0.0454

GnomAD4 exome

AF:

0.0434

AC:

63309

AN:

1458986

Hom.:

1565

Cov.:

AF XY:

0.0426

AC XY:

30908

AN XY:

725762

show subpopulations

African (AFR)

AF:

0.00760

AC:

254

AN:

33424

American (AMR)

AF:

0.0300

AC:

1342

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.0583

AC:

1520

AN:

26092

East Asian (EAS)

AF:

0.000126

AC:

AN:

39656

South Asian (SAS)

AF:

0.00886

AC:

764

AN:

86234

European-Finnish (FIN)

AF:

0.0244

AC:

1266

AN:

51872

Middle Eastern (MID)

AF:

0.0416

AC:

234

AN:

5620

European-Non Finnish (NFE)

AF:

0.0498

AC:

55365

AN:

1111162

Other (OTH)

AF:

0.0425

AC:

2559

AN:

60258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

3194

6388

9583

12777

15971

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2004

4008

6012

8016

10020

<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:

0.0328

AC:

5002

AN:

152296

Hom.:

117

Cov.:

AF XY:

0.0315

AC XY:

2344

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0101

AC:

422

AN:

41578

American (AMR)

AF:

0.0405

AC:

620

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0530

AC:

184

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00767

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0228

AC:

242

AN:

10622

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0493

AC:

3356

AN:

68008

Other (OTH)

AF:

0.0336

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

249

497

746

994

1243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0202

Hom.:

Bravo

AF:

0.0347

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.4

(source)

DANN

Benign

0.74

PhyloP100

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over