NM_017760.7:c.3137G>A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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
• Publications: 0 publications found

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]

NCAPG2 Gene-Disease associations (from GenCC):

• Khan-Khan-Katsanis syndrome

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Illumina, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017760.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAPG2	NM_017760.7	MANE Select	c.3137G>A	p.Arg1046Lys	missense	Exon 25 of 28	NP_060230.5
	NCAPG2	NM_001281933.2		c.3137G>A	p.Arg1046Lys	missense	Exon 25 of 28	NP_001268862.1	Q86XI2-2
	NCAPG2	NM_001281932.2		c.3137G>A	p.Arg1046Lys	missense	Exon 26 of 29	NP_001268861.1	Q86XI2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAPG2	ENST00000356309.8	TSL:1 MANE Select	c.3137G>A	p.Arg1046Lys	missense	Exon 25 of 28	ENSP00000348657.3	Q86XI2-1
	NCAPG2	ENST00000409339.3	TSL:1	c.3137G>A	p.Arg1046Lys	missense	Exon 25 of 28	ENSP00000387007.3	Q86XI2-2
	NCAPG2	ENST00000467785.5	TSL:1	n.2981G>A		non_coding_transcript_exon	Exon 22 of 25

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.083
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.6
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.054
Sift	Benign	0.86	T
Sift4G	Benign	1.0	T
Polyphen		0.030	B
Vest4		0.23
MutPred		0.38		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
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

hg19: chr7-158439194;