rs16914640

Variant names:

• chr12-9669791-C-G
• rs16914640
• NM_013269.6:c.57C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-9669791-C-G
• chr12-9669791-C-T

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 28 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013269.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC2D	NM_013269.6	MANE Select	c.57C>G	p.Asn19Lys	missense	Exon 1 of 5	NP_037401.1
	CLEC2D	NM_001004419.5		c.57C>G	p.Asn19Lys	missense	Exon 1 of 6	NP_001004419.1
	CLEC2D	NM_001197317.3		c.57C>G	p.Asn19Lys	missense	Exon 1 of 4	NP_001184246.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC2D	ENST00000290855.11	TSL:1 MANE Select	c.57C>G	p.Asn19Lys	missense	Exon 1 of 5	ENSP00000290855.6
	CLEC2D	ENST00000261340.11	TSL:1	c.57C>G	p.Asn19Lys	missense	Exon 1 of 6	ENSP00000261340.7
	CLEC2D	ENST00000261339.10	TSL:1	c.57C>G	p.Asn19Lys	missense	Exon 1 of 4	ENSP00000261339.6

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

GnomAD2 exomes AF: 0.143 AC: 35775 AN: 251042 AF XY: 0.135

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 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

African (AFR) AF: 0.477 AC: 15877 AN: 33292

American (AMR) AF: 0.109 AC: 4861 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2650 AN: 26100

East Asian (EAS) AF: 0.00990 AC: 393 AN: 39684

South Asian (SAS) AF: 0.0876 AC: 7542 AN: 86138

European-Finnish (FIN) AF: 0.164 AC: 8756 AN: 53392

Middle Eastern (MID) AF: 0.160 AC: 921 AN: 5758

European-Non Finnish (NFE) AF: 0.140 AC: 155387 AN: 1108296

Other (OTH) AF: 0.151 AC: 9096 AN: 60236

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

African (AFR) AF: 0.462 AC: 19115 AN: 41350

American (AMR) AF: 0.160 AC: 2436 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0963 AC: 334 AN: 3470

East Asian (EAS) AF: 0.0129 AC: 67 AN: 5182

South Asian (SAS) AF: 0.0772 AC: 372 AN: 4816

European-Finnish (FIN) AF: 0.160 AC: 1687 AN: 10518

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9999 AN: 67962

Other (OTH) AF: 0.195 AC: 411 AN: 2106

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 v4.9

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
MetaRNN	Benign	0.00042	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.5
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.019
Sift	Benign	0.19	T
Sift4G	Benign	0.21	T
Polyphen		0.73	P
Vest4		0.12
MutPred		0.29		Gain of catalytic residue at L23 (P = 0)
MPC		0.23
ClinPred		0.0076	T
GERP RS		-3.0
PromoterAI		-0.023	Neutral
Varity_R		0.039
gMVP		0.14
Mutation Taster		=99/1	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: rs16914640; hg19: chr12-9822387; COSMIC: COSV51992909; COSMIC: COSV51992909;