rs1721244

chr2-73902768-G-Achr2-73902768-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218

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]

ACMG classification

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/exons	MANE	UniProt
ACTG2	NM_001615.4	c.255+280G>A		intron_variant		ENST00000345517.8
ACTG2	NM_001199893.2	c.126+1331G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTG2	ENST00000345517.8	c.255+280G>A		intron_variant		1	NM_001615.4	P1

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84765 AN: 151774 Hom.: 24202 Cov.: 31

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

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.: 41 AF XY: 0.577 AC XY: 397749 AN XY: 688842

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.: 31 AF XY: 0.566 AC XY: 42044 AN XY: 74218

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	14
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

Other links and lift over

dbSNP: rs1721244; hg19: chr2-74129895;