dbSNP rs3765986: CLCA2:c.1984+711T>C (chr1-86448489-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_006536.7(CLCA2):c.1984+711T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,214 control chromosomes in the GnomAD database, including 4,961 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 0.25 ( 4961 hom., cov: 32)

Exomes 𝑓: 0.13 ( 0 hom. )

Consequence

CLCA2
NM_006536.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.271

Publications

6 publications found

Variant links:

Genes affected

CLCA2 (HGNC:2016): (chloride channel accessory 2) This gene encodes a member of the calcium-activated chloride channel regulator (CLCR) family of proteins. Members of this family regulate the transport of chloride across the plasma membrane. The encoded protein is autoproteolytically processed to generate N- and C- terminal fragments. Expression of this gene is upregulated by the tumor suppressor protein p53 in response to DNA damage. In breast cancer, expression of this gene is downregulated and the encoded protein may inhibit migration and invasion while promoting mesenchymal-to-epithelial transition in cancer cell lines. [provided by RefSeq, Sep 2016]

CLCA2 Gene-Disease associations (from GenCC):

heart conduction disease
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp

CLCA2 links:

Genome browser will be placed here

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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCA2	NM_006536.7 link	c.1984+711T>C		intron_variant	Intron 11 of 13	ENST00000370565.5	NP_006527.1	Q9UQC9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCA2	ENST00000370565.5 link	c.1984+711T>C		intron_variant	Intron 11 of 13	1	NM_006536.7	ENSP00000359596.4		Q9UQC9
CLCA2	ENST00000498802.1 link	n.335+21T>C		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37274

AN:

152086

Hom.:

4958

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.507

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.383

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.306

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.279

Gnomad OTH

AF:

0.222

GnomAD4 exome

AF:

0.125

AC:

AN:

Hom.:

Cov.:

AF XY:

0.125

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.245

AC:

37310

AN:

152206

Hom.:

4961

Cov.:

AF XY:

0.246

AC XY:

18334

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.147

AC:

6110

AN:

41538

American (AMR)

AF:

0.226

AC:

3463

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

934

AN:

3472

East Asian (EAS)

AF:

0.384

AC:

1988

AN:

5174

South Asian (SAS)

AF:

0.336

AC:

1622

AN:

4830

European-Finnish (FIN)

AF:

0.306

AC:

3238

AN:

10582

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.279

AC:

18947

AN:

67988

Other (OTH)

AF:

0.221

AC:

466

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1411

2823

4234

5646

7057

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.267

Hom.:

2076

Bravo

AF:

0.236

Asia WGS

AF:

0.327

AC:

1136

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.1

(source)

DANN

Benign

0.68

PhyloP100

0.27

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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rs3765986

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over