7-81974555-GAAAA-GAAAAAAAA

Position:

• chr7-81974555-GAAAA-GAAAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000722.4(CACNA2D1):​c.1956-7_1956-4dupTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,197,436 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: CACNA2D1 NM_000722.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195

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]

CACNA2D1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D1	NM_000722.4	c.1956-7_1956-4dupTTTT		splice_region_variant, intron_variant		ENST00000356860.8	NP_000713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA2D1	ENST00000356860.8	c.1956-7_1956-4dupTTTT		splice_region_variant, intron_variant		1	NM_000722.4	ENSP00000349320.3
CACNA2D1	ENST00000443883.2	c.1992-7_1992-4dupTTTT		splice_region_variant, intron_variant		5		ENSP00000409374.2
CACNA2D1	ENST00000705962.1	c.1836-7_1836-4dupTTTT		splice_region_variant, intron_variant				ENSP00000516190.1
CACNA2D1	ENST00000705961.1	c.1722-7_1722-4dupTTTT		splice_region_variant, intron_variant				ENSP00000516189.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD3 exomes AF: 0.0000463 AC: 9 AN: 194206 Hom.: 0 AF XY: 0.0000475 AC XY: 5 AN XY: 105240

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000222

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000415

Gnomad FIN exome AF: 0.0000563

Gnomad NFE exome AF: 0.0000117

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000117 AC: 14 AN: 1197436 Hom.: 0 Cov.: 18 AF XY: 0.0000132 AC XY: 8 AN XY: 605626

Gnomad4 AFR exome AF: 0.0000724

Gnomad4 AMR exome AF: 0.0000479

Gnomad4 ASJ exome AF: 0.0000424

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000260

Gnomad4 FIN exome AF: 0.0000199

Gnomad4 NFE exome AF: 0.00000452

Gnomad4 OTH exome AF: 0.0000395

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3083235; hg19: chr7-81603871;