dbSNP rs77487055: CACNA2D4:c.*1428_*1429insGAG (chr12-1792226-T-TCTC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_172364.5(CACNA2D4):c.*1428_*1429insGAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.44 ( 16508 hom., cov: 0)

Exomes 𝑓: 0.46 ( 2 hom. )

Consequence

CACNA2D4
NM_172364.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.648

Publications

2 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):

CACNA2D4-related retinopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
retinal cone dystrophy 4
Inheritance: Unknown, AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine
cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CACNA2D4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 12-1792226-T-TCTC is Benign according to our data. Variant chr12-1792226-T-TCTC is described in ClinVar as Benign. ClinVar VariationId is 307801.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172364.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA2D4	NM_172364.5	MANE Select	c.1428_1429insGAG		3_prime_UTR	Exon 38 of 38	NP_758952.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CACNA2D4	ENST00000382722.10	TSL:1 MANE Select	c.1428_1429insGAG	3_prime_UTR	Exon 38 of 38	ENSP00000372169.4	Q7Z3S7-1
CACNA2D4	ENST00000537784.5	TSL:1	n.2035_2036insGAG	non_coding_transcript_exon	Exon 15 of 15	ENSP00000440231.2	X6RLU5
CACNA2D4	ENST00000537784.5	TSL:1	n.2035_2036insGAG	3_prime_UTR	Exon 15 of 15	ENSP00000440231.2	X6RLU5

Frequencies

GnomAD3 genomes

AF:

0.436

AC:

66202

AN:

151852

Hom.:

16506

Cov.:

show subpopulations

Gnomad AFR

AF:

0.189

Gnomad AMI

AF:

0.621

Gnomad AMR

AF:

0.396

Gnomad ASJ

AF:

0.588

Gnomad EAS

AF:

0.479

Gnomad SAS

AF:

0.451

Gnomad FIN

AF:

0.549

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.563

Gnomad OTH

AF:

0.425

GnomAD4 exome

AF:

0.464

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.436

AC:

66208

AN:

151970

Hom.:

16508

Cov.:

AF XY:

0.435

AC XY:

32334

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.188

AC:

7812

AN:

41486

American (AMR)

AF:

0.396

AC:

6053

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.588

AC:

2039

AN:

3470

East Asian (EAS)

AF:

0.480

AC:

2471

AN:

5152

South Asian (SAS)

AF:

0.451

AC:

2171

AN:

4818

European-Finnish (FIN)

AF:

0.549

AC:

5794

AN:

10550

Middle Eastern (MID)

AF:

0.558

AC:

164

AN:

294

European-Non Finnish (NFE)

AF:

0.563

AC:

38245

AN:

67896

Other (OTH)

AF:

0.424

AC:

896

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1746

3493

5239

6986

8732

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

626

1252

1878

2504

3130

<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:

0.239

Hom.:

686

Bravo

AF:

0.412

Asia WGS

AF:

0.424

AC:

1478

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cone dystrophy 3 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.65

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over