chr12-9669791-C-G

Position:

• chr12-9669791-C-G

Variant summary

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

The NM_013269.6(CLEC2D):​c.57C>G​(p.Asn19Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,609,426 control chromosomes in the GnomAD database, including 23,083 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.23 (5602 hom., cov: 32)
  • Exomes 𝑓: 0.14 (17481 hom.)
• Consequence: CLEC2D NM_013269.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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]

CLEC2D (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.1648746E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC2D	NM_013269.6	c.57C>G	p.Asn19Lys	missense_variant	1/5	ENST00000290855.11	NP_037401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC2D	ENST00000290855.11	c.57C>G	p.Asn19Lys	missense_variant	1/5	1	NM_013269.6	ENSP00000290855.6

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34496 AN: 151742 Hom.: 5590 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.0527

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.0772

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.196

GnomAD3 exomes AF: 0.143 AC: 35775 AN: 251042 Hom.: 3719 AF XY: 0.135 AC XY: 18337 AN XY: 135700

Gnomad AFR exome AF: 0.472

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.0107

Gnomad SAS exome AF: 0.0834

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.150

GnomAD4 exome AF: 0.141 AC: 205483 AN: 1457566 Hom.: 17481 Cov.: 30 AF XY: 0.139 AC XY: 100565 AN XY: 725442

Gnomad4 AFR exome AF: 0.477

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.00990

Gnomad4 SAS exome AF: 0.0876

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.140

Gnomad4 OTH exome AF: 0.151

GnomAD4 genome AF: 0.227 AC: 34540 AN: 151860 Hom.: 5602 Cov.: 32 AF XY: 0.224 AC XY: 16595 AN XY: 74192

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.0963

Gnomad4 EAS AF: 0.0129

Gnomad4 SAS AF: 0.0772

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.195

Alfa AF: 0.135 Hom.: 1206

Bravo AF: 0.237

TwinsUK AF: 0.135 AC: 502

ALSPAC AF: 0.130 AC: 501

ESP6500AA AF: 0.460 AC: 2026

ESP6500EA AF: 0.145 AC: 1251

ExAC AF: 0.150 AC: 18257

Asia WGS AF: 0.0800 AC: 276 AN: 3478

EpiCase AF: 0.143

EpiControl AF: 0.141

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.12
DANN	Benign	0.64
DEOGEN2	Benign	0.0010	.;T;.;.;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.68	T;T;T;T;T;T
MetaRNN	Benign	0.00042	T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N;N;N;N;N;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.42	N;N;N;N;N;N
REVEL	Benign	0.019
Sift	Benign	0.19	T;T;T;T;T;T
Sift4G	Benign	0.21	T;T;T;T;T;T
Polyphen		0.73	P;B;.;.;.;.
Vest4		0.12
MutPred		0.29		Gain of catalytic residue at L23 (P = 0);Gain of catalytic residue at L23 (P = 0);Gain of catalytic residue at L23 (P = 0);Gain of catalytic residue at L23 (P = 0);Gain of catalytic residue at L23 (P = 0);.;
MPC		0.23
ClinPred		0.0076	T
GERP RS		-3.0
Varity_R		0.039
gMVP		0.14

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: rs16914640; hg19: chr12-9822387; COSMIC: COSV51992909; COSMIC: COSV51992909;