chr2-73901306-C-T

Variant names:

• chr2-73901306-C-T
• rs1050146
• NM_001615.4:c.-6C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.134

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ACTG2	NM_001615.4	c.-6C>T		5_prime_UTR_variant	Exon 2 of 9	ENST00000345517.8	NP_001606.1
ACTG2	NM_001199893.2	c.-6C>T		5_prime_UTR_variant	Exon 2 of 8		NP_001186822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTG2	ENST00000345517	c.-6C>T		5_prime_UTR_variant	Exon 2 of 9	1	NM_001615.4	ENSP00000295137.3

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115773 AN: 152112 Hom.: 44450 Cov.: 34

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

GnomAD2 exomes AF: 0.775 AC: 185184 AN: 239072 AF XY: 0.770

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 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.: 49 AF XY: 0.774 AC XY: 552499 AN XY: 713438

Gnomad4 AFR exome AF: 0.702 AC: 23030 AN: 32824

Gnomad4 AMR exome AF: 0.882 AC: 38160 AN: 43244

Gnomad4 ASJ exome AF: 0.771 AC: 19442 AN: 25210

Gnomad4 EAS exome AF: 0.515 AC: 19935 AN: 38678

Gnomad4 SAS exome AF: 0.699 AC: 58884 AN: 84184

Gnomad4 FIN exome AF: 0.844 AC: 44662 AN: 52938

Gnomad4 NFE exome AF: 0.787 AC: 863136 AN: 1097406

Gnomad4 Remaining exome AF: 0.768 AC: 45550 AN: 59302

GnomAD4 genome AF: 0.761 AC: 115875 AN: 152230 Hom.: 44493 Cov.: 34 AF XY: 0.762 AC XY: 56722 AN XY: 74434

Gnomad4 AFR AF: 0.698 AC: 0.697514 AN: 0.697514

Gnomad4 AMR AF: 0.826 AC: 0.826078 AN: 0.826078

Gnomad4 ASJ AF: 0.761 AC: 0.760945 AN: 0.760945

Gnomad4 EAS AF: 0.566 AC: 0.565881 AN: 0.565881

Gnomad4 SAS AF: 0.696 AC: 0.696399 AN: 0.696399

Gnomad4 FIN AF: 0.852 AC: 0.851848 AN: 0.851848

Gnomad4 NFE AF: 0.791 AC: 0.790516 AN: 0.790516

Gnomad4 OTH AF: 0.775 AC: 0.775307 AN: 0.775307

Alfa AF: 0.777 Hom.: 48725

Bravo AF: 0.759

Asia WGS AF: 0.673 AC: 2343 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.3
DANN	Benign	0.87
Mutation Taster		=300/0	polymorphism (auto)

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: rs1050146; hg19: chr2-74128433;