7-158646554-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_017760.7(NCAPG2):c.3085G>A(p.Val1029Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,571,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

NCAPG2
NM_017760.7 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.703

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.003911078).

BP6

Variant 7-158646554-C-T is Benign according to our data. Variant chr7-158646554-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 218742.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAPG2	NM_017760.7 link	c.3085G>A	p.Val1029Ile	missense_variant	Exon 25 of 28	ENST00000356309.8	NP_060230.5	Q86XI2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAPG2	ENST00000356309.8 link	c.3085G>A	p.Val1029Ile	missense_variant	Exon 25 of 28	1	NM_017760.7	ENSP00000348657.3		Q86XI2-1

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000279

AC:

AN:

204562

Hom.:

AF XY:

0.000284

AC XY:

AN XY:

112616

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000452

Gnomad ASJ exome

AF:

0.00569

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000405

Gnomad OTH exome

AF:

0.000634

GnomAD4 exome

AF:

0.000149

AC:

211

AN:

1418930

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

116

AN XY:

705882

show subpopulations

Gnomad4 AFR exome

AF:

0.0000336

Gnomad4 AMR exome

AF:

0.0000935

Gnomad4 ASJ exome

AF:

0.00515

Gnomad4 EAS exome

AF:

0.0000271

Gnomad4 SAS exome

AF:

0.0000378

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000428

Gnomad4 OTH exome

AF:

0.000479

GnomAD4 genome

AF:

0.000223

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000539

Hom.:

Bravo

AF:

0.000193

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000245

AC:

ExAC

AF:

0.000315

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:1

Oct 18, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Jun 11, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.032

DANN

Benign

0.49

DEOGEN2

Benign

0.071

T;T;.

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.081

.;T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.0039

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.11

N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.37

N;N;N

REVEL

Benign

0.031

Sift

Benign

0.49

T;T;T

Sift4G

Benign

0.23

T;T;T

Polyphen

0.0020

B;B;B

Vest4

0.061

MVP

0.27

MPC

0.31

ClinPred

0.012

GERP RS

-11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.012

gMVP

0.032

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over