7-82066526-TAAAAA-TAA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_000722.4(CACNA2D1):c.659-5_659-3del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0025 in 1,430,140 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00074 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0027 (0 hom.)
• Consequence: CACNA2D1 NM_000722.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.51

Genes affected

CACNA2D1 (HGNC:1399): (calcium voltage-gated channel auxiliary subunit alpha2delta 1) The preproprotein encoded by this gene is cleaved into multiple chains that comprise the alpha-2 and delta subunits of the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. Mutations in this gene can cause cardiac deficiencies, including Brugada syndrome and short QT syndrome. Alternate splicing results in multiple transcript variants, some of which may lack the delta subunit portion. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 7-82066526-TAAA-T is Benign according to our data. Variant chr7-82066526-TAAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1317982.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 83 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA2D1	NM_000722.4	c.659-5_659-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000356860.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA2D1	ENST00000356860.8	c.659-5_659-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000722.4

Frequencies

GnomAD3 genomes AF: 0.000743 AC: 83 AN: 111720 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.000383

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000390

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000802

Gnomad OTH AF: 0.00262

GnomAD3 exomes AF: 0.0128 AC: 1162 AN: 90532 Hom.: 0 AF XY: 0.0127 AC XY: 617 AN XY: 48522

Gnomad AFR exome AF: 0.0255

Gnomad AMR exome AF: 0.0167

Gnomad ASJ exome AF: 0.0107

Gnomad EAS exome AF: 0.0137

Gnomad SAS exome AF: 0.0101

Gnomad FIN exome AF: 0.00804

Gnomad NFE exome AF: 0.0113

Gnomad OTH exome AF: 0.00950

GnomAD4 exome AF: 0.00265 AC: 3498 AN: 1318420 Hom.: 0 AF XY: 0.00270 AC XY: 1756 AN XY: 650940

Gnomad4 AFR exome AF: 0.00851

Gnomad4 AMR exome AF: 0.0102

Gnomad4 ASJ exome AF: 0.00545

Gnomad4 EAS exome AF: 0.00401

Gnomad4 SAS exome AF: 0.00679

Gnomad4 FIN exome AF: 0.00472

Gnomad4 NFE exome AF: 0.00179

Gnomad4 OTH exome AF: 0.00332

GnomAD4 genome AF: 0.000743 AC: 83 AN: 111720 Hom.: 0 Cov.: 27 AF XY: 0.000680 AC XY: 36 AN XY: 52948

Gnomad4 AFR AF: 0.00181

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.000383

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000390

Gnomad4 NFE AF: 0.0000802

Gnomad4 OTH AF: 0.00262

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs370103843; hg19: chr7-81695842;