Variant 12-6526401-A-T 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.2566+30A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 1,613,920 control chromosomes in the GnomAD database, including 431,807 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.79 ( 47682 hom., cov: 30)

Exomes 𝑓: 0.72 ( 384125 hom. )

Consequence

NCAPD2
NM_014865.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.942

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 12-6526401-A-T is Benign according to our data. Variant chr12-6526401-A-T is described in ClinVar as [Benign]. Clinvar id is 1321845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCAPD2	NM_014865.4 linkuse as main transcript	c.2566+30A>T		intron_variant		ENST00000315579.10	NP_055680.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
NCAPD2	ENST00000315579.10 linkuse as main transcript	c.2566+30A>T	intron_variant	1	NM_014865.4	ENSP00000325017	P1
NCAPD2	ENST00000382457.8 linkuse as main transcript	c.2182+30A>T	intron_variant	5		ENSP00000371895
NCAPD2	ENST00000539084.5 linkuse as main transcript	c.*2261+30A>T	intron_variant, NMD_transcript_variant	2		ENSP00000438495
NCAPD2	ENST00000542492.1 linkuse as main transcript	n.499+30A>T	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.785

AC:

119279

AN:

151940

Hom.:

47627

Cov.:

show subpopulations

Gnomad AFR

AF:

0.944

Gnomad AMI

AF:

0.612

Gnomad AMR

AF:

0.797

Gnomad ASJ

AF:

0.713

Gnomad EAS

AF:

0.691

Gnomad SAS

AF:

0.674

Gnomad FIN

AF:

0.750

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.713

Gnomad OTH

AF:

0.755

GnomAD3 exomes

AF:

0.746

AC:

187588

AN:

251462

Hom.:

70757

AF XY:

0.735

AC XY:

99863

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.950

Gnomad AMR exome

AF:

0.862

Gnomad ASJ exome

AF:

0.704

Gnomad EAS exome

AF:

0.684

Gnomad SAS exome

AF:

0.691

Gnomad FIN exome

AF:

0.749

Gnomad NFE exome

AF:

0.710

Gnomad OTH exome

AF:

0.730

GnomAD4 exome

AF:

0.723

AC:

1057524

AN:

1461860

Hom.:

384125

Cov.:

AF XY:

0.721

AC XY:

524342

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.955

Gnomad4 AMR exome

AF:

0.857

Gnomad4 ASJ exome

AF:

0.708

Gnomad4 EAS exome

AF:

0.676

Gnomad4 SAS exome

AF:

0.683

Gnomad4 FIN exome

AF:

0.750

Gnomad4 NFE exome

AF:

0.715

Gnomad4 OTH exome

AF:

0.730

GnomAD4 genome

AF:

0.785

AC:

119396

AN:

152060

Hom.:

47682

Cov.:

AF XY:

0.784

AC XY:

58296

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.944

Gnomad4 AMR

AF:

0.797

Gnomad4 ASJ

AF:

0.713

Gnomad4 EAS

AF:

0.691

Gnomad4 SAS

AF:

0.674

Gnomad4 FIN

AF:

0.750

Gnomad4 NFE

AF:

0.713

Gnomad4 OTH

AF:

0.755

Alfa

AF:

0.750

Hom.:

7950

Bravo

AF:

0.799

Asia WGS

AF:

0.767

AC:

2667

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Microcephaly 21, primary, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.075

DANN

Benign

0.40

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