rs59278883

Variant names:

• chr2-201515105-T-A
• rs59278883
• NM_001168221.2:c.1507-19136A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001168221.2(CATSPERT):​c.1507-19136A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 151,042 control chromosomes in the GnomAD database, including 1,877 homozygotes. 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: 𝑓 0.13 (1877 hom., cov: 30)
• Consequence: CATSPERT NM_001168221.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489
• Publications: 4 publications found

Genes affected

CATSPERT (HGNC:14438): (C2 calcium dependent domain containing 6) An autosomal recessive form of juvenile amyotrophic lateral sclerosis was originally mapped to a region of chromosome 2 that includes this gene. The encoded protein contains a calcium-dependent membrane targeting C2 domain. This domain is often found in proteins that are involved in membrane trafficking and signal transduction. [provided by RefSeq, Jun 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001168221.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPERT	NM_001168221.2	MANE Select	c.1507-19136A>T		intron	N/A	NP_001161693.1
	CATSPERT	NM_152525.6		c.1507-19136A>T		intron	N/A	NP_689738.3
	CATSPERT	NM_001168216.2		c.1163-19136A>T		intron	N/A	NP_001161688.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2CD6	ENST00000439140.6	TSL:1 MANE Select	c.1507-19136A>T		intron	N/A	ENSP00000409937.1
	C2CD6	ENST00000286195.7	TSL:1	c.1507-19136A>T		intron	N/A	ENSP00000286195.3
	C2CD6	ENST00000439802.5	TSL:2	c.1163-19136A>T		intron	N/A	ENSP00000400672.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 19890 AN: 150930 Hom.: 1864 Cov.: 30

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0958

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.0254

Gnomad MID AF: 0.141

Gnomad NFE AF: 0.0757

Gnomad OTH AF: 0.122

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.132 AC: 19929 AN: 151042 Hom.: 1877 Cov.: 30 AF XY: 0.132 AC XY: 9757 AN XY: 73662

African (AFR) AF: 0.242 AC: 9915 AN: 41012

American (AMR) AF: 0.0956 AC: 1449 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 383 AN: 3460

East Asian (EAS) AF: 0.273 AC: 1406 AN: 5150

South Asian (SAS) AF: 0.215 AC: 1029 AN: 4788

European-Finnish (FIN) AF: 0.0254 AC: 261 AN: 10266

Middle Eastern (MID) AF: 0.146 AC: 42 AN: 288

European-Non Finnish (NFE) AF: 0.0757 AC: 5141 AN: 67926

Other (OTH) AF: 0.122 AC: 255 AN: 2090

Alfa AF: 0.103 Hom.: 158

Bravo AF: 0.140

Asia WGS AF: 0.253 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.1
DANN	Benign	0.42
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

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: rs59278883; hg19: chr2-202379828;