rs2280764

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_StrongBA1

The NM_002474.3(MYH11):c.1249-11G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 1,613,218 control chromosomes in the GnomAD database, including 136,001 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 18149 hom., cov: 32)

Exomes 𝑓: 0.39 ( 117852 hom. )

Consequence

MYH11
NM_002474.3 intron

Scores

Splicing: ADA: 0.00003464

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.720

Publications

12 publications found

Variant links:

Genes affected

MYH11 (HGNC:7569): (myosin heavy chain 11) The protein encoded by this gene is a smooth muscle myosin belonging to the myosin heavy chain family. The gene product is a subunit of a hexameric protein that consists of two heavy chain subunits and two pairs of non-identical light chain subunits. It functions as a major contractile protein, converting chemical energy into mechanical energy through the hydrolysis of ATP. A chromosomal rearrangement involving this gene is associated with acute myeloid leukemia of the M4Eo subtype. Mutations in this gene are associated with visceral myopathy, megacystis-microcolon-intestinal hypoperistalsis syndrome 2, and familial thoracic aortic aneurysm 4. [provided by RefSeq, May 2022]

MYH11 Gene-Disease associations (from GenCC):

familial thoracic aortic aneurysm and aortic dissection
Inheritance: AD, Unknown Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
aortic aneurysm, familial thoracic 4
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
megacystis-microcolon-intestinal hypoperistalsis syndrome 2
Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
megacystis-microcolon-intestinal hypoperistalsis syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
congenital heart disease
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
visceral myopathy 2
Inheritance: AD, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

MYH11 links:

LOC124903650 (HGNC:):

LOC124903650 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=-0.85).

BP6

Variant 16-15759739-C-G is Benign according to our data. Variant chr16-15759739-C-G is described in ClinVar as Benign. ClinVar VariationId is 138371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002474.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYH11	NM_002474.3	MANE Select	c.1249-11G>C	intron	N/A	NP_002465.1	P35749-1
MYH11	NM_001040113.2	MANE Plus Clinical	c.1270-11G>C	intron	N/A	NP_001035202.1	P35749-3
MYH11	NM_001040114.2		c.1270-11G>C	intron	N/A	NP_001035203.1	P35749-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYH11	ENST00000300036.6	TSL:1 MANE Select	c.1249-11G>C	intron	N/A	ENSP00000300036.5	P35749-1
MYH11	ENST00000452625.7	TSL:1 MANE Plus Clinical	c.1270-11G>C	intron	N/A	ENSP00000407821.2	P35749-3
MYH11	ENST00000396324.7	TSL:1	c.1270-11G>C	intron	N/A	ENSP00000379616.3	P35749-2

Frequencies

GnomAD3 genomes

AF:

0.467

AC:

70999

AN:

151934

Hom.:

18110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.671

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.389

Gnomad ASJ

AF:

0.378

Gnomad EAS

AF:

0.682

Gnomad SAS

AF:

0.430

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.376

Gnomad OTH

AF:

0.438

GnomAD2 exomes

AF:

0.411

AC:

103052

AN:

250574

AF XY:

0.405

show subpopulations

Gnomad AFR exome

AF:

0.677

Gnomad AMR exome

AF:

0.341

Gnomad ASJ exome

AF:

0.382

Gnomad EAS exome

AF:

0.694

Gnomad FIN exome

AF:

0.346

Gnomad NFE exome

AF:

0.366

Gnomad OTH exome

AF:

0.376

GnomAD4 exome

AF:

0.395

AC:

576816

AN:

1461166

Hom.:

117852

Cov.:

AF XY:

0.394

AC XY:

286661

AN XY:

726898

show subpopulations

African (AFR)

AF:

0.674

AC:

22543

AN:

33464

American (AMR)

AF:

0.345

AC:

15400

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

9998

AN:

26132

East Asian (EAS)

AF:

0.680

AC:

27008

AN:

39692

South Asian (SAS)

AF:

0.408

AC:

35187

AN:

86222

European-Finnish (FIN)

AF:

0.339

AC:

18092

AN:

53408

Middle Eastern (MID)

AF:

0.312

AC:

1735

AN:

5560

European-Non Finnish (NFE)

AF:

0.379

AC:

421584

AN:

1111680

Other (OTH)

AF:

0.419

AC:

25269

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

17700

35401

53101

70802

88502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13586

27172

40758

54344

67930

<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:

0.468

AC:

71095

AN:

152052

Hom.:

18149

Cov.:

AF XY:

0.465

AC XY:

34546

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.671

AC:

27833

AN:

41466

American (AMR)

AF:

0.389

AC:

5942

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.378

AC:

1312

AN:

3472

East Asian (EAS)

AF:

0.681

AC:

3513

AN:

5156

South Asian (SAS)

AF:

0.431

AC:

2075

AN:

4818

European-Finnish (FIN)

AF:

0.339

AC:

3578

AN:

10564

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.376

AC:

25589

AN:

67976

Other (OTH)

AF:

0.442

AC:

934

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1808

3617

5425

7234

9042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

636

1272

1908

2544

3180

<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:

0.410

Hom.:

2452

Bravo

AF:

0.479

Asia WGS

AF:

0.546

AC:

1899

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Aortic aneurysm, familial thoracic 4 (3)

not specified (3)

Familial thoracic aortic aneurysm and aortic dissection (1)

Megacystis-microcolon-intestinal hypoperistalsis syndrome 2 (1)

not provided (1)

Visceral myopathy 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.2

(source)

DANN

Benign

0.41

PhyloP100

-0.72

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000035

dbscSNV1_RF

Benign

0.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over