12-9681032-C-T

Position:

• chr12-9681032-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_013269.6(CLEC2D):​c.171C>T​(p.Ser57=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 1,465,574 control chromosomes in the GnomAD database, including 157,513 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.50 (18862 hom., cov: 32)
  • Exomes 𝑓: 0.46 (138651 hom.)
• Consequence: CLEC2D NM_013269.6 splice_region, synonymous
• Scores: Splicing: ADA: 0.0002424
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588

Genes affected

CLEC2D (HGNC:14351): (C-type lectin domain family 2 member D) This gene encodes a member of the natural killer cell receptor C-type lectin family. The encoded protein inhibits osteoclast formation and contains a transmembrane domain near the N-terminus as well as the C-type lectin-like extracellular domain. Several alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-0.588 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC2D	NM_013269.6	c.171C>T	p.Ser57=	splice_region_variant, synonymous_variant	2/5	ENST00000290855.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC2D	ENST00000290855.11	c.171C>T	p.Ser57=	splice_region_variant, synonymous_variant	2/5	1	NM_013269.6	P2

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75147 AN: 151738 Hom.: 18853 Cov.: 32

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.483

GnomAD3 exomes AF: 0.462 AC: 114739 AN: 248258 Hom.: 27015 AF XY: 0.466 AC XY: 62538 AN XY: 134284

Gnomad AFR exome AF: 0.557

Gnomad AMR exome AF: 0.371

Gnomad ASJ exome AF: 0.504

Gnomad EAS exome AF: 0.389

Gnomad SAS exome AF: 0.477

Gnomad FIN exome AF: 0.542

Gnomad NFE exome AF: 0.465

Gnomad OTH exome AF: 0.472

GnomAD4 exome AF: 0.457 AC: 600745 AN: 1313718 Hom.: 138651 Cov.: 20 AF XY: 0.459 AC XY: 303582 AN XY: 660816

Gnomad4 AFR exome AF: 0.553

Gnomad4 AMR exome AF: 0.378

Gnomad4 ASJ exome AF: 0.504

Gnomad4 EAS exome AF: 0.364

Gnomad4 SAS exome AF: 0.477

Gnomad4 FIN exome AF: 0.531

Gnomad4 NFE exome AF: 0.454

Gnomad4 OTH exome AF: 0.465

GnomAD4 genome AF: 0.495 AC: 75198 AN: 151856 Hom.: 18862 Cov.: 32 AF XY: 0.498 AC XY: 36991 AN XY: 74248

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.478

Alfa AF: 0.471 Hom.: 41373

Bravo AF: 0.485

Asia WGS AF: 0.426 AC: 1479 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00024
dbscSNV1_RF	Benign	0.62
SpliceAI score (max)		0.020		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: rs3764021; hg19: chr12-9833628; COSMIC: COSV51992921;