chr2-65246584-A-G

Position:

• chr2-65246584-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000260641.10(ACTR2):​c.220A>G​(p.Met74Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACTR2 ENST00000260641.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.48

Genes affected

ACTR2 (HGNC:169): (actin related protein 2) The specific function of this gene has not yet been determined; however, the protein it encodes is known to be a major constituent of the ARP2/3 complex. This complex is located at the cell surface and is essential to cell shape and motility through lamellipodial actin assembly and protrusion. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTR2	NM_005722.4	c.220A>G	p.Met74Val	missense_variant	3/9	ENST00000260641.10	NP_005713.1
ACTR2	NM_001005386.3	c.235A>G	p.Met79Val	missense_variant	4/10		NP_001005386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTR2	ENST00000260641.10	c.220A>G	p.Met74Val	missense_variant	3/9	1	NM_005722.4	ENSP00000260641	A1
ACTR2	ENST00000377982.8	c.235A>G	p.Met79Val	missense_variant	4/10	1		ENSP00000367220	P3
ACTR2	ENST00000471552.5	c.*145A>G		3_prime_UTR_variant, NMD_transcript_variant	4/4	4		ENSP00000490923
ACTR2	ENST00000476840.5	c.*150A>G		3_prime_UTR_variant, NMD_transcript_variant	4/4	4		ENSP00000490877

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 27, 2024

The c.235A>G (p.M79V) alteration is located in exon 4 (coding exon 4) of the ACTR2 gene. This alteration results from a A to G substitution at nucleotide position 235, causing the methionine (M) at amino acid position 79 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Uncertain	0.64	D;.;.
Eigen	Benign	0.093
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.46	T;T;T
MetaSVM	Uncertain	0.24	D
MutationAssessor	Benign	1.4	L;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.5	N;D;D
REVEL	Pathogenic	0.74
Sift	Benign	0.39	T;T;T
Sift4G	Benign	0.23	T;T;T
Polyphen		0.0030	B;.;B
Vest4		0.48
MutPred		0.74		Loss of catalytic residue at V70 (P = 0.1655);.;.;
MVP		0.98
MPC		1.4
ClinPred		0.73	D
GERP RS		5.5
Varity_R		0.38
gMVP		0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-65473718;