Genetic Variant CLEC2D:c.357+91T>A (chr12-9688177-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013269.6(CLEC2D):c.357+91T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,277,960 control chromosomes in the GnomAD database, including 116,230 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.35 ( 10815 hom., cov: 29)

Exomes 𝑓: 0.43 ( 105415 hom. )

Consequence

CLEC2D
NM_013269.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0710

Publications

6 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CLEC2D	NM_013269.6	MANE Select	c.357+91T>A	intron	N/A	NP_037401.1
CLEC2D	NM_001004419.5		c.357+91T>A	intron	N/A	NP_001004419.1
CLEC2D	NM_001197317.3		c.246+91T>A	intron	N/A	NP_001184246.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CLEC2D	ENST00000290855.11	TSL:1 MANE Select	c.357+91T>A	intron	N/A	ENSP00000290855.6
CLEC2D	ENST00000261340.11	TSL:1	c.357+91T>A	intron	N/A	ENSP00000261340.7
CLEC2D	ENST00000430909.5	TSL:1	c.294+91T>A	intron	N/A	ENSP00000413045.1

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

52793

AN:

149010

Hom.:

10815

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.464

Gnomad AMR

AF:

0.432

Gnomad ASJ

AF:

0.384

Gnomad EAS

AF:

0.584

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.374

Gnomad MID

AF:

0.379

Gnomad NFE

AF:

0.433

Gnomad OTH

AF:

0.385

GnomAD4 exome

AF:

0.427

AC:

482043

AN:

1128840

Hom.:

105415

Cov.:

AF XY:

0.427

AC XY:

232708

AN XY:

544726

show subpopulations

African (AFR)

AF:

0.129

AC:

2894

AN:

22446

American (AMR)

AF:

0.519

AC:

6828

AN:

13164

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

6276

AN:

15706

East Asian (EAS)

AF:

0.615

AC:

16287

AN:

26464

South Asian (SAS)

AF:

0.395

AC:

13663

AN:

34584

European-Finnish (FIN)

AF:

0.420

AC:

11665

AN:

27790

Middle Eastern (MID)

AF:

0.362

AC:

1491

AN:

4124

European-Non Finnish (NFE)

AF:

0.430

AC:

404229

AN:

939476

Other (OTH)

AF:

0.415

AC:

18710

AN:

45086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

11436

22872

34307

45743

57179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13836

27672

41508

55344

69180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.354

AC:

52809

AN:

149120

Hom.:

10815

Cov.:

AF XY:

0.355

AC XY:

25721

AN XY:

72524

show subpopulations

African (AFR)

AF:

0.147

AC:

6000

AN:

40678

American (AMR)

AF:

0.432

AC:

6423

AN:

14880

Ashkenazi Jewish (ASJ)

AF:

0.384

AC:

1323

AN:

3444

East Asian (EAS)

AF:

0.584

AC:

2979

AN:

5102

South Asian (SAS)

AF:

0.409

AC:

1953

AN:

4772

European-Finnish (FIN)

AF:

0.374

AC:

3507

AN:

9380

Middle Eastern (MID)

AF:

0.366

AC:

107

AN:

292

European-Non Finnish (NFE)

AF:

0.433

AC:

29289

AN:

67602

Other (OTH)

AF:

0.391

AC:

810

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1516

3032

4549

6065

7581

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

520

1040

1560

2080

2600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.396

Hom.:

1622

Bravo

AF:

0.356

Asia WGS

AF:

0.490

AC:

1701

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.1

(source)

DANN

Benign

0.68

PhyloP100

-0.071

PromoterAI

-0.017

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over