2-65268572-G-T

Position:

• chr2-65268572-G-T

Variant summary

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

The NM_005722.4(ACTR2):​c.1023G>T​(p.Lys341Asn) 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 NM_005722.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.78

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.1023G>T	p.Lys341Asn	missense_variant	9/9	ENST00000260641.10	NP_005713.1
ACTR2	NM_001005386.3	c.1038G>T	p.Lys346Asn	missense_variant	10/10		NP_001005386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTR2	ENST00000260641.10	c.1023G>T	p.Lys341Asn	missense_variant	9/9	1	NM_005722.4	ENSP00000260641.5
ACTR2	ENST00000377982.8	c.1038G>T	p.Lys346Asn	missense_variant	10/10	1		ENSP00000367220.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

May 04, 2022

The c.1038G>T (p.K346N) alteration is located in exon 10 (coding exon 10) of the ACTR2 gene. This alteration results from a G to T substitution at nucleotide position 1038, causing the lysine (K) at amino acid position 346 to be replaced by an asparagine (N). 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	Pathogenic	0.92
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D;.;.
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.9	M;.;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.9	D;D;.
REVEL	Uncertain	0.43
Sift	Uncertain	0.0010	D;D;.
Sift4G	Uncertain	0.036	D;D;D
Polyphen		0.94	P;.;.
Vest4		0.71
MutPred		0.66		Loss of methylation at K341 (P = 0.0071);.;.;
MVP		0.64
MPC		1.8
ClinPred		0.98	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.89
gMVP		0.95

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: chr2-65495706;