7-81950272-A-T

Position:

• chr7-81950272-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000722.4(CACNA2D1):​c.*120T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0055 in 1,589,544 control chromosomes in the GnomAD database, including 264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (130 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (134 hom.)
• Consequence: CACNA2D1 NM_000722.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.604

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-81950272-A-T is Benign according to our data. Variant chr7-81950272-A-T is described in ClinVar as [Benign]. Clinvar id is 1226581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D1	NM_000722.4	c.*120T>A		3_prime_UTR_variant	39/39	ENST00000356860.8	NP_000713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA2D1	ENST00000356860.8	c.*120T>A		3_prime_UTR_variant	39/39	1	NM_000722.4	ENSP00000349320
CACNA2D1	ENST00000443883.2	c.*120T>A		3_prime_UTR_variant	39/39	5		ENSP00000409374	P1
CACNA2D1	ENST00000705961.1	c.*120T>A		3_prime_UTR_variant	37/37			ENSP00000516189
CACNA2D1	ENST00000705962.1	c.*120T>A		3_prime_UTR_variant	38/38			ENSP00000516190

Frequencies

GnomAD3 genomes AF: 0.0240 AC: 3645 AN: 152026 Hom.: 125 Cov.: 32

Gnomad AFR AF: 0.0775

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.0283

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.00352 AC: 5058 AN: 1437400 Hom.: 134 Cov.: 27 AF XY: 0.00322 AC XY: 2305 AN XY: 715606

Gnomad4 AFR exome AF: 0.0810

Gnomad4 AMR exome AF: 0.00930

Gnomad4 ASJ exome AF: 0.0209

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00104

Gnomad4 FIN exome AF: 0.0000198

Gnomad4 NFE exome AF: 0.000670

Gnomad4 OTH exome AF: 0.00939

GnomAD4 genome AF: 0.0242 AC: 3677 AN: 152144 Hom.: 130 Cov.: 32 AF XY: 0.0242 AC XY: 1799 AN XY: 74394

Gnomad4 AFR AF: 0.0780

Gnomad4 AMR AF: 0.0150

Gnomad4 ASJ AF: 0.0283

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000927

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0190 Hom.: 14

Bravo AF: 0.0272

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.66
DANN	Benign	0.61

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: rs78368203; hg19: chr7-81579588;