7-158646554-C-T

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

19

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]

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
NCAPG2NM_017760.7 linkc.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
NCAPG2ENST00000356309.8 linkc.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:
34
AN:
152136
Hom.:
0
Cov.:
33
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:
57
AN:
204562
Hom.:
0
AF XY:
0.000284
AC XY:
32
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.:
0
Cov.:
30
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:
34
AN:
152254
Hom.:
0
Cov.:
33
AF XY:
0.000148
AC XY:
11
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.:
0
Bravo
AF:
0.000193
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000245
AC:
2
ExAC
AF:
0.000315
AC:
38

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
T
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
N
LIST_S2
Benign
0.081
.;T;T
M_CAP
Benign
0.0027
T
MetaRNN
Benign
0.0039
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.11
N;N;N
PrimateAI
Benign
0.23
T
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
T
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.

Other links and lift over

dbSNP: rs199598836; hg19: chr7-158439246; API