Variant 2-73901264-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001615.4(ACTG2):c.-36-12G>C variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001833

Clinical Significance

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

Conservation

PhyloP100: -1.08

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1188998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-73901264-G-C is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTG2	NM_001615.4 linkuse as main transcript	c.-36-12G>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000345517.8
ACTG2	NM_001199893.2 linkuse as main transcript	c.-36-12G>C		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTG2	ENST00000345517.8 linkuse as main transcript	c.-36-12G>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001615.4	P1	P63267-1

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

GnomAD3 exomes

AF:

0.762

AC:

134011

AN:

175786

Hom.:

51841

AF XY:

0.758

AC XY:

71303

AN XY:

94100

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 SAS exome

AF:

0.639

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

Gnomad4 AFR exome

AF:

0.701

Gnomad4 AMR exome

AF:

0.875

Gnomad4 ASJ exome

AF:

0.813

Gnomad4 EAS exome

AF:

0.509

Gnomad4 SAS exome

AF:

0.653

Gnomad4 FIN exome

AF:

0.843

Gnomad4 NFE exome

AF:

0.786

Gnomad4 OTH exome

AF:

0.768

GnomAD4 genome

AF:

0.762

AC:

115996

AN:

152176

Hom.:

44594

Cov.:

AF XY:

0.762

AC XY:

56730

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.701

Gnomad4 AMR

AF:

0.826

Gnomad4 ASJ

AF:

0.806

Gnomad4 EAS

AF:

0.569

Gnomad4 SAS

AF:

0.658

Gnomad4 FIN

AF:

0.852

Gnomad4 NFE

AF:

0.791

Gnomad4 OTH

AF:

0.778

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Megacystis-microcolon-intestinal hypoperistalsis syndrome 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Visceral myopathy 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.9

DANN

Benign

0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over