NM_001615.4:c.-36-12G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001615.4(ACTG2):c.-36-12G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 1,500,930 control chromosomes in the GnomAD database, including 450,845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 44594 hom., cov: 33)

Exomes 𝑓: 0.77 ( 406251 hom. )

Consequence

ACTG2
NM_001615.4 intron

Scores

Splicing: ADA: 0.00001833

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.08

Publications

12 publications found

Variant links:

Genes affected

ACTG2 (HGNC:145): (actin gamma 2, smooth muscle) Actins are highly conserved proteins that are involved in various types of cell motility and in the maintenance of the cytoskeleton. Three types of actins, alpha, beta and gamma, have been identified in vertebrates. Alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins co-exist in most cell types as components of the cytoskeleton and as mediators of internal cell motility. This gene encodes actin gamma 2; a smooth muscle actin found in enteric tissues. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Based on similarity to peptide cleavage of related actins, the mature protein of this gene is formed by removal of two N-terminal peptides.[provided by RefSeq, Dec 2010]

ACTG2 Gene-Disease associations (from GenCC):

visceral myopathy 1
Inheritance: AR, AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
familial visceral myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
megacystis-microcolon-intestinal hypoperistalsis syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACTG2 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=-0.94).

BP6

Variant 2-73901264-G-C is Benign according to our data. Variant chr2-73901264-G-C is described in ClinVar as Benign. ClinVar VariationId is 1188998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001615.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTG2	NM_001615.4	MANE Select	c.-36-12G>C		intron	N/A	NP_001606.1
	ACTG2	NM_001199893.2		c.-36-12G>C		intron	N/A	NP_001186822.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ACTG2	ENST00000345517.8	TSL:1 MANE Select	c.-36-12G>C	intron	N/A	ENSP00000295137.3
ACTG2	ENST00000409918.5	TSL:1	c.-36-12G>C	intron	N/A	ENSP00000387182.1
ACTG2	ENST00000409624.1	TSL:2	c.-36-12G>C	intron	N/A	ENSP00000386857.1

Frequencies

GnomAD3 genomes

AF:

0.762

AC:

115894

AN:

152058

Hom.:

44551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.701

Gnomad AMI

AF:

0.749

Gnomad AMR

AF:

0.825

Gnomad ASJ

AF:

0.806

Gnomad EAS

AF:

0.569

Gnomad SAS

AF:

0.658

Gnomad FIN

AF:

0.852

Gnomad MID

AF:

0.782

Gnomad NFE

AF:

0.791

Gnomad OTH

AF:

0.777

GnomAD2 exomes

AF:

0.762

AC:

134011

AN:

175786

AF XY:

0.758

show subpopulations

Gnomad AFR exome

AF:

0.694

Gnomad AMR exome

AF:

0.882

Gnomad ASJ exome

AF:

0.806

Gnomad EAS exome

AF:

0.552

Gnomad FIN exome

AF:

0.850

Gnomad NFE exome

AF:

0.782

Gnomad OTH exome

AF:

0.778

GnomAD4 exome

AF:

0.773

AC:

1043134

AN:

1348754

Hom.:

406251

Cov.:

AF XY:

0.771

AC XY:

509896

AN XY:

661494

show subpopulations

African (AFR)

AF:

0.701

AC:

20694

AN:

29506

American (AMR)

AF:

0.875

AC:

27452

AN:

31360

Ashkenazi Jewish (ASJ)

AF:

0.813

AC:

16803

AN:

20656

East Asian (EAS)

AF:

0.509

AC:

18234

AN:

35822

South Asian (SAS)

AF:

0.653

AC:

46621

AN:

71446

European-Finnish (FIN)

AF:

0.843

AC:

41699

AN:

49464

Middle Eastern (MID)

AF:

0.758

AC:

4048

AN:

5340

European-Non Finnish (NFE)

AF:

0.786

AC:

825083

AN:

1049802

Other (OTH)

AF:

0.768

AC:

42500

AN:

55358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

10143

20286

30430

40573

50716

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20220

40440

60660

80880

101100

<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:

0.762

AC:

115996

AN:

152176

Hom.:

44594

Cov.:

AF XY:

0.762

AC XY:

56730

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.701

AC:

29110

AN:

41502

American (AMR)

AF:

0.826

AC:

12625

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.806

AC:

2799

AN:

3472

East Asian (EAS)

AF:

0.569

AC:

2943

AN:

5174

South Asian (SAS)

AF:

0.658

AC:

3175

AN:

4822

European-Finnish (FIN)

AF:

0.852

AC:

9023

AN:

10592

Middle Eastern (MID)

AF:

0.772

AC:

227

AN:

294

European-Non Finnish (NFE)

AF:

0.791

AC:

53764

AN:

68000

Other (OTH)

AF:

0.778

AC:

1647

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1448

2896

4345

5793

7241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

858

1716

2574

3432

4290

<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:

0.760

Hom.:

5123

Bravo

AF:

0.761

Asia WGS

AF:

0.661

AC:

2302

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 23, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Megacystis-microcolon-intestinal hypoperistalsis syndrome 5

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Visceral myopathy 1

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.9

(source)

DANN

Benign

0.51

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000018

dbscSNV1_RF

Benign

0.028

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over