Variant rs2058111 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_172364.5(CACNA2D4):c.*55A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 1,504,018 control chromosomes in the GnomAD database, including 216,354 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 16908 hom., cov: 33)

Exomes 𝑓: 0.54 ( 199446 hom. )

Consequence

CACNA2D4
NM_172364.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.466

Variant links:

Genes affected

CACNA2D4 (HGNC:20202): (calcium voltage-gated channel auxiliary subunit alpha2delta 4) This gene encodes a member of the alpha-2/delta subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Various versions of each of these subunits exist, either expressed from similar genes or the result of alternative splicing. Research on a highly similar protein in rabbit suggests the protein described in this record is cleaved into alpha-2 and delta subunits. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

CACNA2D4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 12-1793600-T-G is Benign according to our data. Variant chr12-1793600-T-G is described in ClinVar as [Benign]. Clinvar id is 307828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D4	NM_172364.5 linkuse as main transcript	c.*55A>C		3_prime_UTR_variant	38/38	ENST00000382722.10	NP_758952.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA2D4	ENST00000382722.10 linkuse as main transcript	c.*55A>C		3_prime_UTR_variant	38/38	1	NM_172364.5	ENSP00000372169	P2	Q7Z3S7-1

Frequencies

GnomAD3 genomes

AF:

0.446

AC:

67796

AN:

152000

Hom.:

16906

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.622

Gnomad AMR

AF:

0.400

Gnomad ASJ

AF:

0.588

Gnomad EAS

AF:

0.482

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.551

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.432

GnomAD4 exome

AF:

0.539

AC:

728131

AN:

1351900

Hom.:

199446

Cov.:

AF XY:

0.538

AC XY:

365165

AN XY:

678280

show subpopulations

Gnomad4 AFR exome

AF:

0.207

Gnomad4 AMR exome

AF:

0.407

Gnomad4 ASJ exome

AF:

0.590

Gnomad4 EAS exome

AF:

0.522

Gnomad4 SAS exome

AF:

0.457

Gnomad4 FIN exome

AF:

0.544

Gnomad4 NFE exome

AF:

0.561

Gnomad4 OTH exome

AF:

0.524

GnomAD4 genome

AF:

0.446

AC:

67803

AN:

152118

Hom.:

16908

Cov.:

AF XY:

0.446

AC XY:

33133

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.221

Gnomad4 AMR

AF:

0.400

Gnomad4 ASJ

AF:

0.588

Gnomad4 EAS

AF:

0.483

Gnomad4 SAS

AF:

0.453

Gnomad4 FIN

AF:

0.551

Gnomad4 NFE

AF:

0.564

Gnomad4 OTH

AF:

0.430

Alfa

AF:

0.515

Hom.:

8173

Bravo

AF:

0.424

Asia WGS

AF:

0.428

AC:

1492

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Retinal cone dystrophy 4

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.93

DANN

Benign

0.64

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over