rs2072373

Positions:

• chr12-6522722-G-A
• chr12-6522722-G-C

Variant summary

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

The NM_014865.4(NCAPD2):​c.1955-106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,248,248 control chromosomes in the GnomAD database, including 22,675 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 0.18 (2619 hom., cov: 32)
  • Exomes 𝑓: 0.19 (20056 hom.)
• Consequence: NCAPD2 NM_014865.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.843

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCAPD2	NM_014865.4	c.1955-106G>A		intron_variant		ENST00000315579.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCAPD2	ENST00000315579.10	c.1955-106G>A		intron_variant		1	NM_014865.4	P1
NCAPD2	ENST00000382457.8	c.1571-106G>A		intron_variant		5
NCAPD2	ENST00000539084.5	c.*1650-106G>A		intron_variant, NMD_transcript_variant		2
NCAPD2	ENST00000538600.1	n.119-162G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27362 AN: 152088 Hom.: 2617 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.0861

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.172

GnomAD4 exome AF: 0.187 AC: 204461 AN: 1096042 Hom.: 20056 AF XY: 0.184 AC XY: 101506 AN XY: 550850

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.0890

Gnomad4 EAS exome AF: 0.305

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.183

GnomAD4 genome AF: 0.180 AC: 27368 AN: 152206 Hom.: 2619 Cov.: 32 AF XY: 0.180 AC XY: 13408 AN XY: 74410

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.0861

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.170

Alfa AF: 0.166 Hom.: 1286

Bravo AF: 0.181

Asia WGS AF: 0.251 AC: 870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.3
DANN	Benign	0.73

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: rs2072373; hg19: chr12-6631888;