chr12-9922069-G-T

Variant names:

• chr12-9922069-G-T
• rs1464947774
• NM_001130711.2:c.303C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001130711.2(CLEC2A):​c.303C>A​(p.Asp101Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,382,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 7.2e-7 (0 hom.)
• Consequence: CLEC2A NM_001130711.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.75
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05799651).

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.303C>A	p.Asp101Glu	missense	Exon 3 of 5	NP_001124183.1	Q6UVW9-1
	CLEC2A	NM_207375.3		c.303C>A	p.Asp101Glu	missense	Exon 3 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.303C>A	p.Asp101Glu	missense	Exon 3 of 5	ENSP00000396163.1	Q6UVW9-1
	CLEC2A	ENST00000339766.8	TSL:1	c.303C>A	p.Asp101Glu	missense	Exon 3 of 5	ENSP00000339732.4	Q6UVW9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000687 AC: 1 AN: 145472 AF XY: 0.0000131

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000175

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1382998 Hom.: 0 Cov.: 30 AF XY: 0.00000147 AC XY: 1 AN XY: 681030

African (AFR) AF: 0.00 AC: 0 AN: 30614

American (AMR) AF: 0.00 AC: 0 AN: 32284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24494

East Asian (EAS) AF: 0.00 AC: 0 AN: 35582

South Asian (SAS) AF: 0.00 AC: 0 AN: 75696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5604

European-Non Finnish (NFE) AF: 9.33e-7 AC: 1 AN: 1072320

Other (OTH) AF: 0.00 AC: 0 AN: 57368

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	Uncertain	0.43
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.0060
DANN	Benign	0.21
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0021	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.63	N
PhyloP100		-1.8
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.027
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.020	B
Vest4		0.17
MutPred		0.63		Gain of catalytic residue at I96 (P = 0.0676)
MVP		0.081
ClinPred		0.047	T
GERP RS		-4.3
Varity_R		0.064
gMVP		0.089
Mutation Taster		=91/9	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: rs1464947774; hg19: chr12-10074668;