ENST00000444595.6:n.*2255G>C

Variant names:

• chr12-1792998-C-G
• rs2286379
• ENST00000444595.6:n.*2255G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000444595.6(CACNA2D4):​n.*2255G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CACNA2D4 ENST00000444595.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• inherited retinal dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinal cone dystrophy 4

  Inheritance: AR, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA2D4	NM_172364.5	c.*657G>C		3_prime_UTR_variant	Exon 38 of 38	ENST00000382722.10	NP_758952.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA2D4	ENST00000444595.6	n.*2255G>C		non_coding_transcript_exon_variant	Exon 37 of 37	1		ENSP00000403371.2
CACNA2D4	ENST00000537784.5	n.*1264G>C		non_coding_transcript_exon_variant	Exon 15 of 15	1		ENSP00000440231.2
CACNA2D4	ENST00000545595.6	n.*1264G>C		non_coding_transcript_exon_variant	Exon 10 of 10	1		ENSP00000442329.2
CACNA2D4	ENST00000382722.10	c.*657G>C		3_prime_UTR_variant	Exon 38 of 38	1	NM_172364.5	ENSP00000372169.4
CACNA2D4	ENST00000444595.6	n.*2255G>C		3_prime_UTR_variant	Exon 37 of 37	1		ENSP00000403371.2
CACNA2D4	ENST00000537784.5	n.*1264G>C		3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000440231.2
CACNA2D4	ENST00000545595.6	n.*1264G>C		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000442329.2
CACNA2D4	ENST00000587995.5	c.*657G>C		downstream_gene_variant		5		ENSP00000465372.1
CACNA2D4	ENST00000538450.5	c.*657G>C		downstream_gene_variant		2		ENSP00000446341.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 13386

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.17
DANN	Benign	0.41
PhyloP100		-2.1

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: rs2286379; hg19: chr12-1902164;