7-158650893-C-A

Variant names:

• chr7-158650893-C-A
• rs765636505
• NM_017760.7:c.3014G>T

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.3014G>T​(p.Arg1005Leu) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1005W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NCAPG2 NM_017760.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• 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=0.1355105).

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.3014G>T	p.Arg1005Leu	missense	Exon 24 of 28	NP_060230.5
	NCAPG2	NM_001281933.2		c.3014G>T	p.Arg1005Leu	missense	Exon 24 of 28	NP_001268862.1	Q86XI2-2
	NCAPG2	NM_001281932.2		c.3014G>T	p.Arg1005Leu	missense	Exon 25 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.3014G>T	p.Arg1005Leu	missense	Exon 24 of 28	ENSP00000348657.3	Q86XI2-1
	NCAPG2	ENST00000409339.3	TSL:1	c.3014G>T	p.Arg1005Leu	missense	Exon 24 of 28	ENSP00000387007.3	Q86XI2-2
	NCAPG2	ENST00000467785.5	TSL:1	n.2858G>T		non_coding_transcript_exon	Exon 21 of 25

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	10
DANN	Benign	0.95
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.066	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.011
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.056
Sift	Benign	0.17	T
Sift4G	Benign	0.46	T
Polyphen		0.18	B
Vest4		0.45
MutPred		0.44		Loss of disorder (P = 0.0713)
MVP		0.38
MPC		0.62
ClinPred		0.45	T
GERP RS		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.22
Mutation Taster		=96/4	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

dbSNP: rs765636505; hg19: chr7-158443585;