rs367648527

Variant names:

• chr12-9916781-C-A
• rs367648527
• NM_001130711.2:c.329G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-9916781-C-A
• chr12-9916781-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001130711.2(CLEC2A):​c.329G>T​(p.Gly110Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CLEC2A NM_001130711.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.553
• Publications: 0 publications found

Genes affected

CLEC2A (HGNC:24191): (C-type lectin domain family 2 member A) Enables protein homodimerization activity. Predicted to be involved in natural killer cell mediated cytotoxicity. Predicted to act upstream of or within several processes, including T cell receptor signaling pathway; regulation of actin filament polymerization; and regulation of interleukin-2 production. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32717058).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130711.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC2A	NM_001130711.2	MANE Select	c.329G>T	p.Gly110Val	missense	Exon 4 of 5	NP_001124183.1	Q6UVW9-1
	CLEC2A	NM_207375.3		c.329G>T	p.Gly110Val	missense	Exon 4 of 5	NP_997258.1	Q6UVW9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC2A	ENST00000455827.2	TSL:1 MANE Select	c.329G>T	p.Gly110Val	missense	Exon 4 of 5	ENSP00000396163.1	Q6UVW9-1
	CLEC2A	ENST00000339766.8	TSL:1	c.329G>T	p.Gly110Val	missense	Exon 4 of 5	ENSP00000339732.4	Q6UVW9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398620 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 689816

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31564

American (AMR) AF: 0.00 AC: 0 AN: 35692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.00 AC: 0 AN: 35684

South Asian (SAS) AF: 0.00 AC: 0 AN: 79134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078206

Other (OTH) AF: 0.00 AC: 0 AN: 58076

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.55
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-8.1	D
REVEL	Benign	0.051
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.96	D
Vest4		0.33
MutPred		0.51		Gain of catalytic residue at G110 (P = 0.0028)
MVP		0.31
ClinPred		0.98	D
GERP RS		-0.16
Varity_R		0.70
gMVP		0.37
Mutation Taster		=97/3	polymorphism

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: rs367648527; hg19: chr12-10069380;