2-201569730-A-G

Variant names:

• chr2-201569730-A-G
• rs10931959
• NM_001168221.2:c.833+2211T>C

Variant summary

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

The NM_001168221.2(CATSPERT):​c.833+2211T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,982 control chromosomes in the GnomAD database, including 14,330 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 0.42 (14330 hom., cov: 31)
• Consequence: CATSPERT NM_001168221.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPERT	NM_001168221.2	MANE Select	c.833+2211T>C		intron	N/A	NP_001161693.1	Q53TS8-4
	CATSPERT	NM_152525.6		c.833+2211T>C		intron	N/A	NP_689738.3
	CATSPERT	NM_001168217.2		c.833+2211T>C		intron	N/A	NP_001161689.1	Q53TS8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2CD6	ENST00000439140.6	TSL:1 MANE Select	c.833+2211T>C		intron	N/A	ENSP00000409937.1	Q53TS8-4
	C2CD6	ENST00000286195.7	TSL:1	c.833+2211T>C		intron	N/A	ENSP00000286195.3	Q53TS8-1
	C2CD6	ENST00000450242.1	TSL:1	c.833+2211T>C		intron	N/A	ENSP00000399016.1	Q53TS8-3

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64505 AN: 151864 Hom.: 14310 Cov.: 31

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.425 AC: 64559 AN: 151982 Hom.: 14330 Cov.: 31 AF XY: 0.433 AC XY: 32159 AN XY: 74288

African (AFR) AF: 0.339 AC: 14042 AN: 41426

American (AMR) AF: 0.513 AC: 7841 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1558 AN: 3468

East Asian (EAS) AF: 0.751 AC: 3870 AN: 5156

South Asian (SAS) AF: 0.522 AC: 2514 AN: 4812

European-Finnish (FIN) AF: 0.498 AC: 5253 AN: 10558

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28137 AN: 67964

Other (OTH) AF: 0.436 AC: 919 AN: 2108

Alfa AF: 0.424 Hom.: 7854

Bravo AF: 0.424

Asia WGS AF: 0.625 AC: 2170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.3
DANN	Benign	0.58
PhyloP100		0.32
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: rs10931959; hg19: chr2-202434453; COSMIC: COSV107261442;