chr2-73901264-G-C

Variant names:

• chr2-73901264-G-C
• rs1721241
• NM_001615.4:c.-36-12G>C

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.-36-12G>C variant causes a 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 intron
• Scores: Splicing: ADA: 0.00001833
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.08
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• visceral myopathy 1

  Inheritance: AR, AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial visceral myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• megacystis-microcolon-intestinal hypoperistalsis syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1188998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.-36-12G>C		intron_variant	Intron 1 of 8	ENST00000345517.8	NP_001606.1
ACTG2	NM_001199893.2	c.-36-12G>C		intron_variant	Intron 1 of 7		NP_001186822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTG2	ENST00000345517.8	c.-36-12G>C		intron_variant	Intron 1 of 8	1	NM_001615.4	ENSP00000295137.3

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115894 AN: 152058 Hom.: 44551 Cov.: 33

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

GnomAD2 exomes AF: 0.762 AC: 134011 AN: 175786 AF XY: 0.758

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 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.: 31 AF XY: 0.771 AC XY: 509896 AN XY: 661494

African (AFR) AF: 0.701 AC: 20694 AN: 29506

American (AMR) AF: 0.875 AC: 27452 AN: 31360

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 16803 AN: 20656

East Asian (EAS) AF: 0.509 AC: 18234 AN: 35822

South Asian (SAS) AF: 0.653 AC: 46621 AN: 71446

European-Finnish (FIN) AF: 0.843 AC: 41699 AN: 49464

Middle Eastern (MID) AF: 0.758 AC: 4048 AN: 5340

European-Non Finnish (NFE) AF: 0.786 AC: 825083 AN: 1049802

Other (OTH) AF: 0.768 AC: 42500 AN: 55358

GnomAD4 genome AF: 0.762 AC: 115996 AN: 152176 Hom.: 44594 Cov.: 33 AF XY: 0.762 AC XY: 56730 AN XY: 74406

African (AFR) AF: 0.701 AC: 29110 AN: 41502

American (AMR) AF: 0.826 AC: 12625 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 2799 AN: 3472

East Asian (EAS) AF: 0.569 AC: 2943 AN: 5174

South Asian (SAS) AF: 0.658 AC: 3175 AN: 4822

European-Finnish (FIN) AF: 0.852 AC: 9023 AN: 10592

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.791 AC: 53764 AN: 68000

Other (OTH) AF: 0.778 AC: 1647 AN: 2116

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

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	-0.94
CADD	Benign	1.9
DANN	Benign	0.51
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1721241; hg19: chr2-74128391; COSMIC: COSV61828474;