rs758739

Variant names:

• chr12-6517203-G-C
• rs758739
• NM_014865.4:c.1186-162G>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.1186-162G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 152,186 control chromosomes in the GnomAD database, including 46,201 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 0.77 (46201 hom., cov: 32)
• Consequence: NCAPD2 NM_014865.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 12 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAPD2	NM_014865.4	c.1186-162G>C		intron_variant	Intron 10 of 31	ENST00000315579.10	NP_055680.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAPD2	ENST00000315579.10	c.1186-162G>C		intron_variant	Intron 10 of 31	1	NM_014865.4	ENSP00000325017.5
NCAPD2	ENST00000382457.8	c.802-162G>C		intron_variant	Intron 7 of 20	5		ENSP00000371895.4
NCAPD2	ENST00000539084.5	n.*881-162G>C		intron_variant	Intron 9 of 30	2		ENSP00000438495.1
NCAPD2	ENST00000536090.1	n.-156G>C		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117742 AN: 152068 Hom.: 46152 Cov.: 32

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.774 AC: 117853 AN: 152186 Hom.: 46201 Cov.: 32 AF XY: 0.774 AC XY: 57588 AN XY: 74390

African (AFR) AF: 0.908 AC: 37711 AN: 41544

American (AMR) AF: 0.792 AC: 12092 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2473 AN: 3470

East Asian (EAS) AF: 0.690 AC: 3570 AN: 5174

South Asian (SAS) AF: 0.673 AC: 3250 AN: 4826

European-Finnish (FIN) AF: 0.756 AC: 7989 AN: 10572

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.712 AC: 48433 AN: 68006

Other (OTH) AF: 0.746 AC: 1577 AN: 2114

Alfa AF: 0.763 Hom.: 5555

Bravo AF: 0.786

Asia WGS AF: 0.765 AC: 2659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.014
DANN	Benign	0.38
PhyloP100		-1.5
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: rs758739; hg19: chr12-6626369;