rs917634

chr12-6522003-C-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.27

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]

ACMG classification

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	UniProt
NCAPD2	NM_014865.4	c.1920C>A	p.Ile640=	synonymous_variant	15/32	ENST00000315579.10

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76541 AN: 151920 Hom.: 19638 Cov.: 32

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

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.: 42 AF XY: 0.455 AC XY: 331177 AN XY: 727078

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.: 32 AF XY: 0.502 AC XY: 37319 AN XY: 74314

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:2

Revision: criteria provided, multiple submitters, no conflicts

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

clinical testing

GeneDx

May 06, 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

Other links and lift over

dbSNP: rs917634; hg19: chr12-6631169; COSMIC: COSV59698353; COSMIC: COSV59698353;