Variant 12-6528679-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014865.4(NCAPD2):c.3300T>C(p.Arg1100=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 1,607,368 control chromosomes in the GnomAD database, including 429,779 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 47652 hom., cov: 31)

Exomes 𝑓: 0.72 ( 382127 hom. )

Consequence

NCAPD2
NM_014865.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0001095

Clinical Significance

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

Conservation

PhyloP100: 0.690

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 12-6528679-T-C is Benign according to our data. Variant chr12-6528679-T-C is described in ClinVar as [Benign]. Clinvar id is 1321846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.69 with no splicing effect.

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.3300T>C	p.Arg1100=	splice_region_variant, synonymous_variant	26/32	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.3300T>C	p.Arg1100=	splice_region_variant, synonymous_variant	26/32	1	NM_014865.4	ENSP00000325017	P1
NCAPD2	ENST00000535804.1 linkuse as main transcript	n.133T>C		non_coding_transcript_exon_variant	1/2	3
NCAPD2	ENST00000539084.5 linkuse as main transcript	c.*2995T>C		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	25/31	2		ENSP00000438495

Frequencies

GnomAD3 genomes

AF:

0.785

AC:

119244

AN:

151948

Hom.:

47597

Cov.:

show subpopulations

Gnomad AFR

AF:

0.944

Gnomad AMI

AF:

0.613

Gnomad AMR

AF:

0.797

Gnomad ASJ

AF:

0.712

Gnomad EAS

AF:

0.677

Gnomad SAS

AF:

0.673

Gnomad FIN

AF:

0.751

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.713

Gnomad OTH

AF:

0.757

GnomAD3 exomes

AF:

0.745

AC:

186624

AN:

250596

Hom.:

70310

AF XY:

0.733

AC XY:

99305

AN XY:

135392

show subpopulations

Gnomad AFR exome

AF:

0.950

Gnomad AMR exome

AF:

0.862

Gnomad ASJ exome

AF:

0.703

Gnomad EAS exome

AF:

0.667

Gnomad SAS exome

AF:

0.690

Gnomad FIN exome

AF:

0.750

Gnomad NFE exome

AF:

0.711

Gnomad OTH exome

AF:

0.730

GnomAD4 exome

AF:

0.723

AC:

1052289

AN:

1455300

Hom.:

382127

Cov.:

AF XY:

0.721

AC XY:

520689

AN XY:

722480

show subpopulations

Gnomad4 AFR exome

AF:

0.955

Gnomad4 AMR exome

AF:

0.857

Gnomad4 ASJ exome

AF:

0.708

Gnomad4 EAS exome

AF:

0.664

Gnomad4 SAS exome

AF:

0.681

Gnomad4 FIN exome

AF:

0.750

Gnomad4 NFE exome

AF:

0.715

Gnomad4 OTH exome

AF:

0.729

GnomAD4 genome

AF:

0.785

AC:

119360

AN:

152068

Hom.:

47652

Cov.:

AF XY:

0.784

AC XY:

58287

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.944

Gnomad4 AMR

AF:

0.797

Gnomad4 ASJ

AF:

0.712

Gnomad4 EAS

AF:

0.677

Gnomad4 SAS

AF:

0.672

Gnomad4 FIN

AF:

0.751

Gnomad4 NFE

AF:

0.713

Gnomad4 OTH

AF:

0.757

Alfa

AF:

0.720

Hom.:

92332

Bravo

AF:

0.798

Asia WGS

AF:

0.762

AC:

2649

AN:

3478

EpiCase

AF:

0.705

EpiControl

AF:

0.691

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

-0.47

CADD

Benign

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.016

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