NM_000722.4:c.1516-10delT

Variant names:

• chr7-82005506-GA-G
• rs576139922
• NM_000722.4:c.1516-10delT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000722.4(CACNA2D1):​c.1516-10delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0372 in 91,472 control chromosomes in the GnomAD database, including 46 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (46 hom., cov: 31)
  • Exomes 𝑓: 0.26 (28 hom.)
  • Failed GnomAD Quality Control
• Consequence: CACNA2D1 NM_000722.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.00

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 Benign. Variant got -16 ACMG points.

• BP6: Variant 7-82005506-GA-G is Benign according to our data. Variant chr7-82005506-GA-G is described in ClinVar as [Benign]. Clinvar id is 416574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-82005506-GA-G is described in Lovd as [Benign]. Variant chr7-82005506-GA-G is described in Lovd as [Likely_benign]. Variant chr7-82005506-GA-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA2D1	NM_000722.4	c.1516-10delT		intron_variant	Intron 17 of 38	ENST00000356860.8	NP_000713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA2D1	ENST00000356860.8	c.1516-10delT		intron_variant	Intron 17 of 38	1	NM_000722.4	ENSP00000349320.3

Frequencies

GnomAD3 genomes AF: 0.0371 AC: 3396 AN: 91420 Hom.: 46 Cov.: 31

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0190

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.0181

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.0247

Gnomad NFE AF: 0.0324

Gnomad OTH AF: 0.0315

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.256 AC: 223865 AN: 872830 Hom.: 28 Cov.: 0 AF XY: 0.259 AC XY: 111134 AN XY: 429818

Gnomad4 AFR exome AF: 0.241

Gnomad4 AMR exome AF: 0.269

Gnomad4 ASJ exome AF: 0.274

Gnomad4 EAS exome AF: 0.305

Gnomad4 SAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.217

Gnomad4 NFE exome AF: 0.256

Gnomad4 OTH exome AF: 0.273

GnomAD4 genome AF: 0.0372 AC: 3399 AN: 91472 Hom.: 46 Cov.: 31 AF XY: 0.0376 AC XY: 1661 AN XY: 44122

Gnomad4 AFR AF: 0.0583

Gnomad4 AMR AF: 0.0190

Gnomad4 ASJ AF: 0.0271

Gnomad4 EAS AF: 0.00304

Gnomad4 SAS AF: 0.0185

Gnomad4 FIN AF: 0.0386

Gnomad4 NFE AF: 0.0324

Gnomad4 OTH AF: 0.0313

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 28, 2016

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Nov 08, 2023

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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: rs576139922; hg19: chr7-81634822;