chr12-9913680-C-T

Variant names:

• chr12-9913680-C-T
• rs142033208
• NM_001130711.2:c.411G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001130711.2(CLEC2A):​c.411G>A​(p.Trp137*) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000562 in 1,538,826 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (2 hom.)
• Consequence: CLEC2A NM_001130711.2 stop_gained, splice_region
• Scores: Splicing: ADA: 0.03183
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.04
• Publications: 2 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 -6 ACMG points.

• BP6: Variant 12-9913680-C-T is Benign according to our data. Variant chr12-9913680-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2642698.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.411G>A	p.Trp137*	stop_gained splice_region	Exon 5 of 5	NP_001124183.1	Q6UVW9-1
	CLEC2A	NM_207375.3		c.410+3020G>A		intron	N/A	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.411G>A	p.Trp137*	stop_gained splice_region	Exon 5 of 5	ENSP00000396163.1	Q6UVW9-1
	CLEC2A	ENST00000339766.8	TSL:1	c.410+3020G>A		intron	N/A	ENSP00000339732.4	Q6UVW9-2

Frequencies

GnomAD3 genomes AF: 0.00273 AC: 416 AN: 152122 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00927

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000715 AC: 104 AN: 145458 AF XY: 0.000517

Gnomad AFR exome AF: 0.0110

Gnomad AMR exome AF: 0.000636

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000517

Gnomad OTH exome AF: 0.000239

GnomAD4 exome AF: 0.000323 AC: 448 AN: 1386586 Hom.: 2 Cov.: 26 AF XY: 0.000300 AC XY: 205 AN XY: 684278

African (AFR) AF: 0.0103 AC: 322 AN: 31178

American (AMR) AF: 0.000746 AC: 26 AN: 34846

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24988

East Asian (EAS) AF: 0.00 AC: 0 AN: 35634

South Asian (SAS) AF: 0.0000256 AC: 2 AN: 78072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45454

Middle Eastern (MID) AF: 0.00124 AC: 7 AN: 5664

European-Non Finnish (NFE) AF: 0.0000466 AC: 50 AN: 1073110

Other (OTH) AF: 0.000711 AC: 41 AN: 57640

GnomAD4 genome AF: 0.00274 AC: 417 AN: 152240 Hom.: 4 Cov.: 32 AF XY: 0.00249 AC XY: 185 AN XY: 74442

African (AFR) AF: 0.00927 AC: 385 AN: 41528

American (AMR) AF: 0.00144 AC: 22 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68016

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00144 Hom.: 12

Bravo AF: 0.00308

ESP6500AA AF: 0.0108 AC: 15

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00167 AC: 36

Asia WGS AF: 0.00144 AC: 5 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Pathogenic	0.54
CADD	Pathogenic	37
DANN	Uncertain	0.99
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Benign	0.43	N
M_CAP	Benign	0.0028	T
PhyloP100		1.0
Vest4		0.14
GERP RS		2.6
Mutation Taster		=45/155	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.032
dbscSNV1_RF	Benign	0.34
SpliceAI score (max)		0.18		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: rs142033208; hg19: chr12-10066279;