chr7-82153198-A-G

Variant names:

• chr7-82153198-A-G
• rs6942458
• NM_000722.4:c.355-16522T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000722.4(CACNA2D1):​c.355-16522T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,184 control chromosomes in the GnomAD database, including 6,504 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6504 hom., cov: 27)
• Consequence: CACNA2D1 NM_000722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• short QT syndrome

  Inheritance: AD Classification: SUPPORTIVE, NO_KNOWN Submitted by: ClinGen, Orphanet
• Brugada syndrome

  Inheritance: AD, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Genomics England PanelApp
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• developmental and epileptic encephalopathy 110

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Brugada syndrome 1

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000722.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA2D1	NM_000722.4	MANE Select	c.355-16522T>C		intron	N/A	NP_000713.2
	CACNA2D1	NM_001366867.1		c.355-16522T>C		intron	N/A	NP_001353796.1
	CACNA2D1	NM_001302890.2		c.355-16522T>C		intron	N/A	NP_001289819.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA2D1	ENST00000356860.8	TSL:1 MANE Select	c.355-16522T>C		intron	N/A	ENSP00000349320.3
	CACNA2D1	ENST00000423588.1	TSL:1	c.355-16522T>C		intron	N/A	ENSP00000405395.1
	CACNA2D1	ENST00000443883.2	TSL:5	c.355-16522T>C		intron	N/A	ENSP00000409374.2

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42053 AN: 151066 Hom.: 6486 Cov.: 27

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.263

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.279 AC: 42108 AN: 151184 Hom.: 6504 Cov.: 27 AF XY: 0.280 AC XY: 20654 AN XY: 73782

African (AFR) AF: 0.430 AC: 17686 AN: 41138

American (AMR) AF: 0.225 AC: 3402 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 825 AN: 3460

East Asian (EAS) AF: 0.162 AC: 834 AN: 5140

South Asian (SAS) AF: 0.278 AC: 1330 AN: 4778

European-Finnish (FIN) AF: 0.252 AC: 2630 AN: 10446

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14617 AN: 67810

Other (OTH) AF: 0.269 AC: 562 AN: 2092

Alfa AF: 0.233 Hom.: 13515

Bravo AF: 0.280

Asia WGS AF: 0.246 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.41
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6942458; hg19: chr7-81782514;