dbSNP rs1721244: ACTG2:c.*40G>A (chr2-73902768-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000409918.5(ACTG2):c.*40G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,548,380 control chromosomes in the GnomAD database, including 261,461 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.56 ( 24220 hom., cov: 31)

Exomes 𝑓: 0.58 ( 237241 hom. )

Consequence

ACTG2
ENST00000409918.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.218

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTG2	NM_001615.4 link	c.255+280G>A		intron_variant	Intron 3 of 8	ENST00000345517.8	NP_001606.1	P63267-1
ACTG2	NM_001199893.2 link	c.126+1331G>A		intron_variant	Intron 2 of 7		NP_001186822.1	P63267-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTG2	ENST00000345517.8 link	c.255+280G>A		intron_variant	Intron 3 of 8	1	NM_001615.4	ENSP00000295137.3		P63267-1

Frequencies

GnomAD3 genomes

AF:

0.558

AC:

84765

AN:

151774

Hom.:

24202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.455

Gnomad AMI

AF:

0.554

Gnomad AMR

AF:

0.653

Gnomad ASJ

AF:

0.436

Gnomad EAS

AF:

0.487

Gnomad SAS

AF:

0.518

Gnomad FIN

AF:

0.714

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.591

Gnomad OTH

AF:

0.562

GnomAD3 exomes

AF:

0.596

AC:

89417

AN:

149968

Hom.:

27566

AF XY:

0.585

AC XY:

46969

AN XY:

80316

show subpopulations

Gnomad AFR exome

AF:

0.447

Gnomad AMR exome

AF:

0.766

Gnomad ASJ exome

AF:

0.453

Gnomad EAS exome

AF:

0.500

Gnomad SAS exome

AF:

0.505

Gnomad FIN exome

AF:

0.717

Gnomad NFE exome

AF:

0.585

Gnomad OTH exome

AF:

0.574

GnomAD4 exome

AF:

0.580

AC:

809412

AN:

1396488

Hom.:

237241

Cov.:

AF XY:

0.577

AC XY:

397749

AN XY:

688842

show subpopulations

Gnomad4 AFR exome

AF:

0.448

Gnomad4 AMR exome

AF:

0.748

Gnomad4 ASJ exome

AF:

0.453

Gnomad4 EAS exome

AF:

0.433

Gnomad4 SAS exome

AF:

0.499

Gnomad4 FIN exome

AF:

0.704

Gnomad4 NFE exome

AF:

0.588

Gnomad4 OTH exome

AF:

0.561

GnomAD4 genome

AF:

0.558

AC:

84831

AN:

151892

Hom.:

24220

Cov.:

AF XY:

0.566

AC XY:

42044

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.455

Gnomad4 AMR

AF:

0.653

Gnomad4 ASJ

AF:

0.436

Gnomad4 EAS

AF:

0.486

Gnomad4 SAS

AF:

0.519

Gnomad4 FIN

AF:

0.714

Gnomad4 NFE

AF:

0.591

Gnomad4 OTH

AF:

0.564

Alfa

AF:

0.576

Hom.:

44321

Bravo

AF:

0.552

Asia WGS

AF:

0.552

AC:

1921

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

DANN

Benign

0.76

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over