12-6513180-T-C

Variant names:

• chr12-6513180-T-C
• rs2079868
• NM_014865.4:c.588-1085T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014865.4(NCAPD2):​c.588-1085T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 151,970 control chromosomes in the GnomAD database, including 38,460 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.71 (38460 hom., cov: 31)
• Consequence: NCAPD2 NM_014865.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• microcephaly 21, primary, autosomal recessive

  Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAPD2	NM_014865.4	c.588-1085T>C		intron_variant	Intron 6 of 31	ENST00000315579.10	NP_055680.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAPD2	ENST00000315579.10	c.588-1085T>C		intron_variant	Intron 6 of 31	1	NM_014865.4	ENSP00000325017.5
NCAPD2	ENST00000382457.8	c.204-1085T>C		intron_variant	Intron 3 of 20	5		ENSP00000371895.4
NCAPD2	ENST00000539084.5	n.*283-1085T>C		intron_variant	Intron 5 of 30	2		ENSP00000438495.1
NCAPD2	ENST00000545732.1	n.29-1085T>C		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107829 AN: 151852 Hom.: 38436 Cov.: 31

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.702

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.710 AC: 107899 AN: 151970 Hom.: 38460 Cov.: 31 AF XY: 0.706 AC XY: 52461 AN XY: 74266

African (AFR) AF: 0.742 AC: 30754 AN: 41420

American (AMR) AF: 0.733 AC: 11200 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2243 AN: 3468

East Asian (EAS) AF: 0.544 AC: 2798 AN: 5144

South Asian (SAS) AF: 0.625 AC: 3004 AN: 4804

European-Finnish (FIN) AF: 0.698 AC: 7366 AN: 10556

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.711 AC: 48359 AN: 67986

Other (OTH) AF: 0.696 AC: 1466 AN: 2106

Alfa AF: 0.718 Hom.: 14058

Bravo AF: 0.718

Asia WGS AF: 0.639 AC: 2221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.88
DANN	Benign	0.69
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2079868; hg19: chr12-6622346;