Variant 12-6528950-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_014865.4(NCAPD2):c.3483C>T(p.Asn1161Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,613,344 control chromosomes in the GnomAD database, including 65,096 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9648 hom., cov: 32)

Exomes 𝑓: 0.27 ( 55448 hom. )

Consequence

NCAPD2
NM_014865.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.19

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:

NCAPD2 (HGNC:):

NCAPD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 12-6528950-C-T is Benign according to our data. Variant chr12-6528950-C-T is described in ClinVar as [Benign]. Clinvar id is 1321847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 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.3483C>T	p.Asn1161Asn	synonymous_variant	27/32	ENST00000315579.10	NP_055680.3	Q15021B3KY03B3KMS0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NCAPD2	ENST00000315579.10 linkuse as main transcript	c.3483C>T	p.Asn1161Asn	synonymous_variant	27/32	1	NM_014865.4	ENSP00000325017.5	Q15021
NCAPD2	ENST00000535804.1 linkuse as main transcript	n.316C>T		non_coding_transcript_exon_variant	2/2	3
NCAPD2	ENST00000539084.5 linkuse as main transcript	n.*3178C>T		non_coding_transcript_exon_variant	26/31	2		ENSP00000438495.1	F5H431
NCAPD2	ENST00000539084.5 linkuse as main transcript	n.*3178C>T		3_prime_UTR_variant	26/31	2		ENSP00000438495.1	F5H431

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51373

AN:

151930

Hom.:

9633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.501

Gnomad AMI

AF:

0.250

Gnomad AMR

AF:

0.354

Gnomad ASJ

AF:

0.421

Gnomad EAS

AF:

0.224

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.370

GnomAD3 exomes

AF:

0.303

AC:

76109

AN:

251430

Hom.:

12496

AF XY:

0.295

AC XY:

40069

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.509

Gnomad AMR exome

AF:

0.411

Gnomad ASJ exome

AF:

0.413

Gnomad EAS exome

AF:

0.226

Gnomad SAS exome

AF:

0.255

Gnomad FIN exome

AF:

0.235

Gnomad NFE exome

AF:

0.268

Gnomad OTH exome

AF:

0.312

GnomAD4 exome

AF:

0.269

AC:

392959

AN:

1461296

Hom.:

55448

Cov.:

AF XY:

0.268

AC XY:

195083

AN XY:

726996

show subpopulations

Gnomad4 AFR exome

AF:

0.521

Gnomad4 AMR exome

AF:

0.406

Gnomad4 ASJ exome

AF:

0.419

Gnomad4 EAS exome

AF:

0.213

Gnomad4 SAS exome

AF:

0.253

Gnomad4 FIN exome

AF:

0.238

Gnomad4 NFE exome

AF:

0.255

Gnomad4 OTH exome

AF:

0.294

GnomAD4 genome

AF:

0.338

AC:

51425

AN:

152048

Hom.:

9648

Cov.:

AF XY:

0.336

AC XY:

24980

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.501

Gnomad4 AMR

AF:

0.354

Gnomad4 ASJ

AF:

0.421

Gnomad4 EAS

AF:

0.224

Gnomad4 SAS

AF:

0.253

Gnomad4 FIN

AF:

0.238

Gnomad4 NFE

AF:

0.262

Gnomad4 OTH

AF:

0.366

Alfa

AF:

0.309

Hom.:

5622

Bravo

AF:

0.358

Asia WGS

AF:

0.279

AC:

973

AN:

3478

EpiCase

AF:

0.290

EpiControl

AF:

0.287

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

-0.43

CADD

Benign

5.9

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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