Genetic Variant NCAPG2:p.Ser1056Ser (chr7-158646471-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_017760.7(NCAPG2):c.3168G>A(p.Ser1056Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00246 in 1,599,408 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0026 ( 12 hom. )

Consequence

NCAPG2
NM_017760.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -3.25

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 7-158646471-C-T is Benign according to our data. Variant chr7-158646471-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3024927.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.25 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAPG2	NM_017760.7 link	c.3168G>A	p.Ser1056Ser	synonymous_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.3168G>A	p.Ser1056Ser	synonymous_variant	Exon 25 of 28	1	NM_017760.7	ENSP00000348657.3		Q86XI2-1

Frequencies

GnomAD3 genomes

AF:

0.00162

AC:

246

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00268

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00159

AC:

377

AN:

236588

Hom.:

AF XY:

0.00180

AC XY:

231

AN XY:

128686

show subpopulations

Gnomad AFR exome

AF:

0.000476

Gnomad AMR exome

AF:

0.00132

Gnomad ASJ exome

AF:

0.00287

Gnomad EAS exome

AF:

0.0000599

Gnomad SAS exome

AF:

0.00101

Gnomad FIN exome

AF:

0.000141

Gnomad NFE exome

AF:

0.00238

Gnomad OTH exome

AF:

0.00157

GnomAD4 exome

AF:

0.00255

AC:

3696

AN:

1447158

Hom.:

Cov.:

AF XY:

0.00258

AC XY:

1858

AN XY:

720064

show subpopulations

Gnomad4 AFR exome

AF:

0.000372

Gnomad4 AMR exome

AF:

0.00118

Gnomad4 ASJ exome

AF:

0.00294

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.00119

Gnomad4 FIN exome

AF:

0.000244

Gnomad4 NFE exome

AF:

0.00297

Gnomad4 OTH exome

AF:

0.00259

GnomAD4 genome

AF:

0.00161

AC:

245

AN:

152250

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

114

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00268

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00248

Hom.:

Bravo

AF:

0.00157

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NCAPG2: BP4, BP7, BS2 -

NCAPG2-related disorder

Benign:1

Aug 08, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.040

DANN

Benign

0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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