chr7-158646502-C-T

Variant names:

• chr7-158646502-C-T
• NM_017760.7:c.3137G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017760.7(NCAPG2):​c.3137G>A​(p.Arg1046Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NCAPG2 NM_017760.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56

Genes affected

NCAPG2 (HGNC:21904): (non-SMC condensin II complex subunit G2) This gene encodes a protein that belongs to the Condensin2nSMC family of proteins. The encoded protein is a regulatory subunit of the condensin II complex which, along with the condensin I complex, plays a role in chromosome assembly and segregation during mitosis. A similar protein in mouse is required for early development of the embryo. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14264718).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAPG2	NM_017760.7	c.3137G>A	p.Arg1046Lys	missense_variant	Exon 25 of 28	ENST00000356309.8	NP_060230.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAPG2	ENST00000356309.8	c.3137G>A	p.Arg1046Lys	missense_variant	Exon 25 of 28	1	NM_017760.7	ENSP00000348657.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3137G>A (p.R1046K) alteration is located in exon 25 (coding exon 24) of the NCAPG2 gene. This alteration results from a G to A substitution at nucleotide position 3137, causing the arginine (R) at amino acid position 1046 to be replaced by a lysine (K). 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	0.16
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Benign	0.89
DEOGEN2	Benign	0.092	T;T;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.083
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.75	.;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M;M
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.43	N;N;N
REVEL	Benign	0.054
Sift	Benign	0.86	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.030	B;B;B
Vest4		0.23
MutPred		0.38		Gain of methylation at R1046 (P = 0.0042);Gain of methylation at R1046 (P = 0.0042);Gain of methylation at R1046 (P = 0.0042);
MVP		0.51
MPC		0.39
ClinPred		0.72	D
GERP RS		4.5
Varity_R		0.084
gMVP		0.29

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: chr7-158439194;