Variant 12-6510118-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014865.4(NCAPD2):c.247C>G(p.Gln83Glu) variant causes a missense change. The variant allele was found at a frequency of 0.738 in 1,608,940 control chromosomes in the GnomAD database, including 441,391 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.79 ( 48494 hom., cov: 32)

Exomes 𝑓: 0.73 ( 392897 hom. )

Consequence

NCAPD2
NM_014865.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.83

Variant links:

Genes affected

NCAPD2 (HGNC:24305): (non-SMC condensin I complex subunit D2) Enables histone binding activity. Involved in mitotic chromosome condensation. Located in condensed chromosome; cytosol; and nucleoplasm. Part of condensin complex. Colocalizes with cytoplasm and nuclear chromosome. Implicated in primary autosomal recessive microcephaly. [provided by Alliance of Genome Resources, Apr 2022]

NCAPD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.7810513E-7).

BP6

Variant 12-6510118-C-G is Benign according to our data. Variant chr12-6510118-C-G is described in ClinVar as [Benign]. Clinvar id is 1321844.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCAPD2	NM_014865.4 linkuse as main transcript	c.247C>G	p.Gln83Glu	missense_variant	4/32	ENST00000315579.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCAPD2	ENST00000315579.10 linkuse as main transcript	c.247C>G	p.Gln83Glu	missense_variant	4/32	1	NM_014865.4	P1

Frequencies

GnomAD3 genomes

AF:

0.792

AC:

120398

AN:

152044

Hom.:

48437

Cov.:

show subpopulations

Gnomad AFR

AF:

0.947

Gnomad AMI

AF:

0.639

Gnomad AMR

AF:

0.803

Gnomad ASJ

AF:

0.720

Gnomad EAS

AF:

0.667

Gnomad SAS

AF:

0.685

Gnomad FIN

AF:

0.765

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.723

Gnomad OTH

AF:

0.767

GnomAD3 exomes

AF:

0.753

AC:

189024

AN:

251158

Hom.:

71959

AF XY:

0.742

AC XY:

100721

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.952

Gnomad AMR exome

AF:

0.866

Gnomad ASJ exome

AF:

0.712

Gnomad EAS exome

AF:

0.653

Gnomad SAS exome

AF:

0.699

Gnomad FIN exome

AF:

0.762

Gnomad NFE exome

AF:

0.723

Gnomad OTH exome

AF:

0.740

GnomAD4 exome

AF:

0.733

AC:

1067489

AN:

1456776

Hom.:

392897

Cov.:

AF XY:

0.731

AC XY:

529596

AN XY:

724966

show subpopulations

Gnomad4 AFR exome

AF:

0.957

Gnomad4 AMR exome

AF:

0.861

Gnomad4 ASJ exome

AF:

0.715

Gnomad4 EAS exome

AF:

0.654

Gnomad4 SAS exome

AF:

0.691

Gnomad4 FIN exome

AF:

0.765

Gnomad4 NFE exome

AF:

0.726

Gnomad4 OTH exome

AF:

0.738

GnomAD4 genome

AF:

0.792

AC:

120517

AN:

152164

Hom.:

48494

Cov.:

AF XY:

0.792

AC XY:

58886

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.947

Gnomad4 AMR

AF:

0.803

Gnomad4 ASJ

AF:

0.720

Gnomad4 EAS

AF:

0.667

Gnomad4 SAS

AF:

0.684

Gnomad4 FIN

AF:

0.765

Gnomad4 NFE

AF:

0.723

Gnomad4 OTH

AF:

0.766

Alfa

AF:

0.723

Hom.:

27316

Bravo

AF:

0.805

TwinsUK

AF:

0.735

AC:

2724

ALSPAC

AF:

0.729

AC:

2809

ESP6500AA

AF:

0.943

AC:

4154

ESP6500EA

AF:

0.716

AC:

6159

ExAC

AF:

0.753

AC:

91465

Asia WGS

AF:

0.768

AC:

2672

AN:

3478

EpiCase

AF:

0.713

EpiControl

AF:

0.703

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 10, 2022	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Microcephaly 21, primary, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.038

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.0092

T;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.15

T;T

MetaRNN

Benign

5.8e-7

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-2.2

N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.96

N;N

REVEL

Benign

0.13

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.021

MPC

0.20

ClinPred

0.0086

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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