12-1800379-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_172364.5(CACNA2D4):c.2921+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

CACNA2D4
NM_172364.5 splice_region, intron

Scores

Splicing: ADA: 0.00003756

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.332

Publications

1 publications found

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 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

CACNA2D4 links:

LOC105369602 (HGNC:):

LOC105369602 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 12-1800379-C-T is Benign according to our data. Variant chr12-1800379-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3691687.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA2D4	NM_172364.5 link	c.2921+7G>A		splice_region_variant, intron_variant	Intron 32 of 37	ENST00000382722.10	NP_758952.4	Q7Z3S7-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNA2D4	ENST00000382722.10 link	c.2921+7G>A	splice_region_variant, intron_variant	Intron 32 of 37	1	NM_172364.5	ENSP00000372169.4	Q7Z3S7-1
CACNA2D4	ENST00000586184.5 link	c.2921+7G>A	splice_region_variant, intron_variant	Intron 32 of 36	5		ENSP00000465060.1	Q7Z3S7-5
CACNA2D4	ENST00000587995.5 link	c.2846+7G>A	splice_region_variant, intron_variant	Intron 31 of 36	5		ENSP00000465372.1	K7EJY1
CACNA2D4	ENST00000585708.5 link	c.2729+7G>A	splice_region_variant, intron_variant	Intron 32 of 36	5		ENSP00000467697.1	Q7Z3S7-6
CACNA2D4	ENST00000588077.5 link	c.2729+7G>A	splice_region_variant, intron_variant	Intron 32 of 37	5		ENSP00000468530.1	Q7Z3S7-4
CACNA2D4	ENST00000536846.6 link	c.359+7G>A	splice_region_variant, intron_variant	Intron 6 of 11	5		ENSP00000468167.1	K7ER98
CACNA2D4	ENST00000538027.6 link	c.356+7G>A	splice_region_variant, intron_variant	Intron 6 of 11	5		ENSP00000443038.2	X6RLY7
CACNA2D4	ENST00000538450.5 link	c.311+7G>A	splice_region_variant, intron_variant	Intron 5 of 10	2		ENSP00000446341.1	B4DVU4
CACNA2D4	ENST00000444595.6 link	n.*1105+7G>A	splice_region_variant, intron_variant	Intron 31 of 36	1		ENSP00000403371.2	E7EUE0
CACNA2D4	ENST00000537784.5 link	n.*114+7G>A	splice_region_variant, intron_variant	Intron 9 of 14	1		ENSP00000440231.2	X6RLU5
CACNA2D4	ENST00000545595.6 link	n.*114+7G>A	splice_region_variant, intron_variant	Intron 4 of 9	1		ENSP00000442329.2	Q7Z3S7-7
CACNA2D4	ENST00000585385.5 link	n.*114+7G>A	splice_region_variant, intron_variant	Intron 5 of 10	5		ENSP00000467333.1	K7EIY9

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41420

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 27, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.6

(source)

DANN

Benign

0.46

PhyloP100

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000038

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over