chr1-86428558-C-T

Variant names:

• chr1-86428558-C-T
• rs72720125
• NM_006536.7:c.465C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_006536.7(CLCA2):​c.465C>T​(p.Tyr155Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,612,924 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (5 hom.)
• Consequence: CLCA2 NM_006536.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.499
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 1-86428558-C-T is Benign according to our data. Variant chr1-86428558-C-T is described in ClinVar as Benign. ClinVar VariationId is 773147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.499 with no splicing effect.
• BS2: High AC in GnomAd4 at 172 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006536.7. 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
	CLCA2	NM_006536.7	MANE Select	c.465C>T	p.Tyr155Tyr	synonymous	Exon 3 of 14	NP_006527.1	Q9UQC9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCA2	ENST00000370565.5	TSL:1 MANE Select	c.465C>T	p.Tyr155Tyr	synonymous	Exon 3 of 14	ENSP00000359596.4	Q9UQC9

Frequencies

GnomAD3 genomes AF: 0.00113 AC: 172 AN: 152152 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00198

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00100 AC: 251 AN: 250294 AF XY: 0.000998

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.000436

Gnomad ASJ exome AF: 0.0000999

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00189

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.00162 AC: 2360 AN: 1460654 Hom.: 5 Cov.: 31 AF XY: 0.00161 AC XY: 1170 AN XY: 726584

African (AFR) AF: 0.000359 AC: 12 AN: 33430

American (AMR) AF: 0.000448 AC: 20 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26066

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39670

South Asian (SAS) AF: 0.0000697 AC: 6 AN: 86094

European-Finnish (FIN) AF: 0.0000750 AC: 4 AN: 53334

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5762

European-Non Finnish (NFE) AF: 0.00200 AC: 2228 AN: 1111332

Other (OTH) AF: 0.00136 AC: 82 AN: 60332

GnomAD4 genome AF: 0.00113 AC: 172 AN: 152270 Hom.: 0 Cov.: 33 AF XY: 0.000967 AC XY: 72 AN XY: 74468

African (AFR) AF: 0.000481 AC: 20 AN: 41538

American (AMR) AF: 0.000523 AC: 8 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00198 AC: 135 AN: 68012

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00130 Hom.: 0

Bravo AF: 0.00111

Asia WGS AF: 0.000289 AC: 2 AN: 3478

EpiCase AF: 0.00180

EpiControl AF: 0.00178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	6.3
DANN	Benign	0.53
PhyloP100		0.50
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs72720125; hg19: chr1-86894241;