Variant 12-6522003-C-A 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.1920C>A(p.Ile640=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,613,514 control chromosomes in the GnomAD database, including 175,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19657 hom., cov: 32)

Exomes 𝑓: 0.46 ( 155907 hom. )

Consequence

NCAPD2
NM_014865.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.27

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 12-6522003-C-A is Benign according to our data. Variant chr12-6522003-C-A is described in ClinVar as [Benign]. Clinvar id is 1238523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.27 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 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.1920C>A	p.Ile640=	synonymous_variant	15/32	ENST00000315579.10	NP_055680.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
NCAPD2	ENST00000315579.10 linkuse as main transcript	c.1920C>A	p.Ile640=	synonymous_variant	15/32	1	NM_014865.4	ENSP00000325017	P1
NCAPD2	ENST00000382457.8 linkuse as main transcript	c.1536C>A	p.Ile512=	synonymous_variant	12/21	5		ENSP00000371895
NCAPD2	ENST00000538600.1 linkuse as main transcript	n.84C>A		non_coding_transcript_exon_variant	1/3	3
NCAPD2	ENST00000539084.5 linkuse as main transcript	c.*1615C>A		3_prime_UTR_variant, NMD_transcript_variant	14/31	2		ENSP00000438495

Frequencies

GnomAD3 genomes

AF:

0.504

AC:

76541

AN:

151920

Hom.:

19638

Cov.:

show subpopulations

Gnomad AFR

AF:

0.586

Gnomad AMI

AF:

0.455

Gnomad AMR

AF:

0.551

Gnomad ASJ

AF:

0.505

Gnomad EAS

AF:

0.557

Gnomad SAS

AF:

0.378

Gnomad FIN

AF:

0.450

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.457

Gnomad OTH

AF:

0.526

GnomAD3 exomes

AF:

0.488

AC:

122716

AN:

251428

Hom.:

30618

AF XY:

0.476

AC XY:

64727

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.587

Gnomad AMR exome

AF:

0.610

Gnomad ASJ exome

AF:

0.500

Gnomad EAS exome

AF:

0.566

Gnomad SAS exome

AF:

0.384

Gnomad FIN exome

AF:

0.450

Gnomad NFE exome

AF:

0.459

Gnomad OTH exome

AF:

0.481

GnomAD4 exome

AF:

0.459

AC:

671004

AN:

1461476

Hom.:

155907

Cov.:

AF XY:

0.455

AC XY:

331177

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.598

Gnomad4 AMR exome

AF:

0.607

Gnomad4 ASJ exome

AF:

0.508

Gnomad4 EAS exome

AF:

0.518

Gnomad4 SAS exome

AF:

0.375

Gnomad4 FIN exome

AF:

0.452

Gnomad4 NFE exome

AF:

0.452

Gnomad4 OTH exome

AF:

0.477

GnomAD4 genome

AF:

0.504

AC:

76592

AN:

152038

Hom.:

19657

Cov.:

AF XY:

0.502

AC XY:

37319

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.585

Gnomad4 AMR

AF:

0.551

Gnomad4 ASJ

AF:

0.505

Gnomad4 EAS

AF:

0.558

Gnomad4 SAS

AF:

0.378

Gnomad4 FIN

AF:

0.450

Gnomad4 NFE

AF:

0.457

Gnomad4 OTH

AF:

0.521

Alfa

AF:

0.471

Hom.:

40431

Bravo

AF:

0.521

Asia WGS

AF:

0.505

AC:

1756

AN:

3478

EpiCase

AF:

0.468

EpiControl

AF:

0.457

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	May 06, 2021	- -
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

BayesDel_noAF

Benign

-0.32

CADD

Benign

8.0

DANN

Benign

0.61

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