dbSNP rs367960608: CACNA2D1:c.3160-13_3160-9delTTTTT (chr7-81950516-TAAAAA-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000722.4(CACNA2D1):c.3160-13_3160-9delTTTTT variant causes a intron change. The variant allele was found at a frequency of 0.000000765 in 1,306,680 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

CACNA2D1
NM_000722.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.16

Publications

1 publications found

Variant links:

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]

CACNA2D1 Gene-Disease associations (from GenCC):

short QT syndrome
Inheritance: AD Classification: SUPPORTIVE, NO_KNOWN Submitted by: ClinGen, Orphanet
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
developmental and epileptic encephalopathy 110
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
Brugada syndrome
Inheritance: Unknown, AD Classification: LIMITED, NO_KNOWN Submitted by: Genomics England PanelApp, Ambry Genetics
Brugada syndrome 1
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

CACNA2D1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000722.4. 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
	CACNA2D1	NM_000722.4	MANE Select	c.3160-13_3160-9delTTTTT		intron	N/A	NP_000713.2	P54289-2
	CACNA2D1	NM_001366867.1		c.3196-13_3196-9delTTTTT		intron	N/A	NP_001353796.1	P54289-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CACNA2D1	ENST00000356860.8	TSL:1 MANE Select	c.3160-13_3160-9delTTTTT	intron	N/A	ENSP00000349320.3	P54289-2
CACNA2D1	ENST00000443883.2	TSL:5	c.3196-13_3196-9delTTTTT	intron	N/A	ENSP00000409374.2	H0Y715
CACNA2D1	ENST00000957014.1		c.3181-13_3181-9delTTTTT	intron	N/A	ENSP00000627073.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000624

AC:

AN:

160184

AF XY:

0.0000116

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000134

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.65e-7

AC:

AN:

1306680

Hom.:

AF XY:

0.00000154

AC XY:

AN XY:

649862

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29362

American (AMR)

AF:

0.00

AC:

AN:

37566

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22378

East Asian (EAS)

AF:

0.00

AC:

AN:

34360

South Asian (SAS)

AF:

0.00

AC:

AN:

74048

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47192

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5198

European-Non Finnish (NFE)

AF:

9.97e-7

AC:

AN:

1003426

Other (OTH)

AF:

0.00

AC:

AN:

53150

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over