rs142849270

Positions:

• chr7-82136680-CAA-C
• chr7-82136680-CAA-CA
• chr7-82136680-CAA-CAAA
• chr7-82136680-CAA-CAAAA
• chr7-82136680-CAA-CAAAAA
• chr7-82136680-CAA-CAAAAAAA
• chr7-82136680-CAA-CAAAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_000722.4(CACNA2D1):​c.355-6_355-5del 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 0.0000227 in 1,188,914 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 Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000023 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CACNA2D1 NM_000722.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.39

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 -5 ACMG points.

• BP6: Variant 7-82136680-CAA-C is Benign according to our data. Variant chr7-82136680-CAA-C is described in Lovd as [Benign].
• BS2: High AC in GnomAdExome4 at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D1	NM_000722.4	c.355-6_355-5del		splice_region_variant, splice_polypyrimidine_tract_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.355-6_355-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000722.4	ENSP00000349320

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 139246 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000120 AC: 14 AN: 116500 Hom.: 0 AF XY: 0.000112 AC XY: 7 AN XY: 62424

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000230

Gnomad SAS exome AF: 0.000138

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000191

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000227 AC: 27 AN: 1188914 Hom.: 0 AF XY: 0.0000204 AC XY: 12 AN XY: 589280

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000304

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000272

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 139246 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 67236

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs142849270; hg19: chr7-81765996;