rs1043262

chr12-6529922-A-Gchr12-6529922-A-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_014865.4(NCAPD2):c.3801A>G(p.Val1267=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 1,613,992 control chromosomes in the GnomAD database, including 428,983 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.77 (45947 hom., cov: 34)
  • Exomes 𝑓: 0.72 (383036 hom.)
• Consequence: NCAPD2 NM_014865.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.700

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 12-6529922-A-G is Benign according to our data. Variant chr12-6529922-A-G is described in ClinVar as [Benign]. Clinvar id is 1321849.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.7 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCAPD2	NM_014865.4	c.3801A>G	p.Val1267=	synonymous_variant	29/32	ENST00000315579.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCAPD2	ENST00000315579.10	c.3801A>G	p.Val1267=	synonymous_variant	29/32	1	NM_014865.4	P1
NCAPD2	ENST00000539885.1	n.482A>G		non_coding_transcript_exon_variant	2/3	3
NCAPD2	ENST00000539084.5	c.*3496A>G		3_prime_UTR_variant, NMD_transcript_variant	28/31	2

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117493 AN: 152098 Hom.: 45896 Cov.: 34

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.749

GnomAD3 exomes AF: 0.744 AC: 186921 AN: 251378 Hom.: 70100 AF XY: 0.733 AC XY: 99623 AN XY: 135860

Gnomad AFR exome AF: 0.901

Gnomad AMR exome AF: 0.860

Gnomad ASJ exome AF: 0.703

Gnomad EAS exome AF: 0.693

Gnomad SAS exome AF: 0.691

Gnomad FIN exome AF: 0.753

Gnomad NFE exome AF: 0.711

Gnomad OTH exome AF: 0.730

GnomAD4 exome AF: 0.723 AC: 1056491 AN: 1461776 Hom.: 383036 Cov.: 65 AF XY: 0.720 AC XY: 523942 AN XY: 727202

Gnomad4 AFR exome AF: 0.907

Gnomad4 AMR exome AF: 0.854

Gnomad4 ASJ exome AF: 0.708

Gnomad4 EAS exome AF: 0.686

Gnomad4 SAS exome AF: 0.683

Gnomad4 FIN exome AF: 0.754

Gnomad4 NFE exome AF: 0.715

Gnomad4 OTH exome AF: 0.727

GnomAD4 genome AF: 0.773 AC: 117606 AN: 152216 Hom.: 45947 Cov.: 34 AF XY: 0.772 AC XY: 57471 AN XY: 74410

Gnomad4 AFR AF: 0.898

Gnomad4 AMR AF: 0.791

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.756

Gnomad4 NFE AF: 0.713

Gnomad4 OTH AF: 0.749

Alfa AF: 0.727 Hom.: 19205

Bravo AF: 0.784

Asia WGS AF: 0.766 AC: 2665 AN: 3478

EpiCase AF: 0.705

EpiControl AF: 0.691

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.82
Cadd	Benign	2.0
Dann	Benign	0.64

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: rs1043262; hg19: chr12-6639088; COSMIC: COSV57522340; COSMIC: COSV57522340;