Variant chr12-6511229-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_014865.4(NCAPD2):c.564A>C(p.Ser188=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,614,136 control chromosomes in the GnomAD database, including 197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 21 hom., cov: 32)

Exomes 𝑓: 0.010 ( 176 hom. )

Consequence

NCAPD2
NM_014865.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.201

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 12-6511229-A-C is Benign according to our data. Variant chr12-6511229-A-C is described in ClinVar as [Benign]. Clinvar id is 1879223.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.201 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.011 (1682/152286) while in subpopulation AMR AF= 0.00974 (149/15304). AF 95% confidence interval is 0.00868. There are 21 homozygotes in gnomad4. There are 965 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCAPD2	NM_014865.4 linkuse as main transcript	c.564A>C	p.Ser188=	synonymous_variant	6/32	ENST00000315579.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCAPD2	ENST00000315579.10 linkuse as main transcript	c.564A>C	p.Ser188=	synonymous_variant	6/32	1	NM_014865.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

1684

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.00975

Gnomad ASJ

AF:

0.0685

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0474

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.00928

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.0118

AC:

2977

AN:

251416

Hom.:

AF XY:

0.0117

AC XY:

1596

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00428

Gnomad ASJ exome

AF:

0.0609

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00235

Gnomad FIN exome

AF:

0.0431

Gnomad NFE exome

AF:

0.00962

Gnomad OTH exome

AF:

0.0157

GnomAD4 exome

AF:

0.0103

AC:

15085

AN:

1461850

Hom.:

176

Cov.:

AF XY:

0.0102

AC XY:

7429

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00179

Gnomad4 AMR exome

AF:

0.00452

Gnomad4 ASJ exome

AF:

0.0613

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00224

Gnomad4 FIN exome

AF:

0.0401

Gnomad4 NFE exome

AF:

0.00896

Gnomad4 OTH exome

AF:

0.0129

GnomAD4 genome

AF:

0.0110

AC:

1682

AN:

152286

Hom.:

Cov.:

AF XY:

0.0130

AC XY:

965

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00168

Gnomad4 AMR

AF:

0.00974

Gnomad4 ASJ

AF:

0.0685

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.0474

Gnomad4 NFE

AF:

0.00928

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.0126

Hom.:

Bravo

AF:

0.00749

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0108

EpiControl

AF:

0.0103

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2024

NCAPD2: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.3

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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