rs2079867

Positions:

• chr12-6512945-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014865.4(NCAPD2):​c.588-1320A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,056 control chromosomes in the GnomAD database, including 46,716 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 0.78 (46716 hom., cov: 31)
• Consequence: NCAPD2 NM_014865.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCAPD2	NM_014865.4	c.588-1320A>G		intron_variant		ENST00000315579.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCAPD2	ENST00000315579.10	c.588-1320A>G		intron_variant		1	NM_014865.4	P1
NCAPD2	ENST00000382457.8	c.204-1320A>G		intron_variant		5
NCAPD2	ENST00000539084.5	c.*283-1320A>G		intron_variant, NMD_transcript_variant		2
NCAPD2	ENST00000545732.1	n.29-1320A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118440 AN: 151936 Hom.: 46664 Cov.: 31

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.780 AC: 118554 AN: 152056 Hom.: 46716 Cov.: 31 AF XY: 0.780 AC XY: 57925 AN XY: 74294

Gnomad4 AFR AF: 0.905

Gnomad4 AMR AF: 0.797

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.683

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.723

Gnomad4 OTH AF: 0.756

Alfa AF: 0.735 Hom.: 44391

Bravo AF: 0.791

Asia WGS AF: 0.766 AC: 2662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	9.5
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2079867; hg19: chr12-6622111;