Variant 2-73901306-C-T 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.-6C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 1,591,700 control chromosomes in the GnomAD database, including 480,554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 44493 hom., cov: 34)

Exomes 𝑓: 0.78 ( 436061 hom. )

Consequence

ACTG2
NM_001615.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.134

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=-0.7).

BP6

Variant 2-73901306-C-T is Benign according to our data. Variant chr2-73901306-C-T is described in ClinVar as [Benign]. Clinvar id is 1188856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-73901306-C-T 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.-6C>T		5_prime_UTR_variant	2/9	ENST00000345517.8
ACTG2	NM_001199893.2 linkuse as main transcript	c.-6C>T		5_prime_UTR_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTG2	ENST00000345517.8 linkuse as main transcript	c.-6C>T		5_prime_UTR_variant	2/9	1	NM_001615.4	P1	P63267-1

Frequencies

GnomAD3 genomes

AF:

0.761

AC:

115773

AN:

152112

Hom.:

44450

Cov.:

show subpopulations

Gnomad AFR

AF:

0.697

Gnomad AMI

AF:

0.749

Gnomad AMR

AF:

0.826

Gnomad ASJ

AF:

0.761

Gnomad EAS

AF:

0.566

Gnomad SAS

AF:

0.696

Gnomad FIN

AF:

0.852

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.790

Gnomad OTH

AF:

0.774

GnomAD3 exomes

AF:

0.775

AC:

185184

AN:

239072

Hom.:

72720

AF XY:

0.770

AC XY:

99544

AN XY:

129244

show subpopulations

Gnomad AFR exome

AF:

0.698

Gnomad AMR exome

AF:

0.889

Gnomad ASJ exome

AF:

0.776

Gnomad EAS exome

AF:

0.565

Gnomad SAS exome

AF:

0.703

Gnomad FIN exome

AF:

0.851

Gnomad NFE exome

AF:

0.789

Gnomad OTH exome

AF:

0.785

GnomAD4 exome

AF:

0.776

AC:

1117109

AN:

1439470

Hom.:

436061

Cov.:

AF XY:

0.774

AC XY:

552499

AN XY:

713438

show subpopulations

Gnomad4 AFR exome

AF:

0.702

Gnomad4 AMR exome

AF:

0.882

Gnomad4 ASJ exome

AF:

0.771

Gnomad4 EAS exome

AF:

0.515

Gnomad4 SAS exome

AF:

0.699

Gnomad4 FIN exome

AF:

0.844

Gnomad4 NFE exome

AF:

0.787

Gnomad4 OTH exome

AF:

0.768

GnomAD4 genome

AF:

0.761

AC:

115875

AN:

152230

Hom.:

44493

Cov.:

AF XY:

0.762

AC XY:

56722

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.698

Gnomad4 AMR

AF:

0.826

Gnomad4 ASJ

AF:

0.761

Gnomad4 EAS

AF:

0.566

Gnomad4 SAS

AF:

0.696

Gnomad4 FIN

AF:

0.852

Gnomad4 NFE

AF:

0.791

Gnomad4 OTH

AF:

0.775

Alfa

AF:

0.779

Hom.:

32369

Bravo

AF:

0.759

Asia WGS

AF:

0.673

AC:

2343

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Megacystis-microcolon-intestinal hypoperistalsis syndrome 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 23, 2018

- -

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

-0.70

CADD

Benign

9.3

DANN

Benign

0.87

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over