Genetic Variant NM_017760.7:c.3235G>A (chr7-158645564-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017760.7(NCAPG2):c.3235G>A(p.Val1079Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

NCAPG2
NM_017760.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.472

Publications

0 publications found

Variant links:

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)

NCAPG2 links:

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ACMG classification

Classification was made for transcript

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=0.20885667).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NCAPG2	NM_017760.7	MANE Select	c.3235G>A	p.Val1079Met	missense	Exon 26 of 28	NP_060230.5
NCAPG2	NM_001281933.2		c.3235G>A	p.Val1079Met	missense	Exon 26 of 28	NP_001268862.1	Q86XI2-2
NCAPG2	NM_001281932.2		c.3235G>A	p.Val1079Met	missense	Exon 27 of 29	NP_001268861.1	Q86XI2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NCAPG2	ENST00000356309.8	TSL:1 MANE Select	c.3235G>A	p.Val1079Met	missense	Exon 26 of 28	ENSP00000348657.3	Q86XI2-1
NCAPG2	ENST00000409339.3	TSL:1	c.3235G>A	p.Val1079Met	missense	Exon 26 of 28	ENSP00000387007.3	Q86XI2-2
NCAPG2	ENST00000467785.5	TSL:1	n.3079G>A		non_coding_transcript_exon	Exon 23 of 25

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.83

M_CAP

Benign

0.014

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

0.47

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.55

REVEL

Benign

0.062

Sift

Benign

0.23

Sift4G

Benign

0.21

Polyphen

0.89

Vest4

0.20

MutPred

0.23

Loss of catalytic residue at V1079 (P = 0.0959)

MVP

0.54

MPC

0.41

ClinPred

0.27

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.024

gMVP

0.17

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over