chr2-201491297-C-A

Variant names:

• chr2-201491297-C-A
• rs200411331
• NM_001168221.2:c.5044G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001168221.2(CATSPERT):​c.5044G>T​(p.Ala1682Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1682T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CATSPERT NM_001168221.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03246969).

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.5044G>T	p.Ala1682Ser	missense	Exon 15 of 16	NP_001161693.1	Q53TS8-4
	CATSPERT	NM_152525.6		c.1582-3395G>T		intron	N/A	NP_689738.3
	CATSPERT	NM_001168216.2		c.*50-3395G>T		intron	N/A	NP_001161688.1	Q53TS8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2CD6	ENST00000439140.6	TSL:1 MANE Select	c.5044G>T	p.Ala1682Ser	missense	Exon 15 of 16	ENSP00000409937.1	Q53TS8-4
	C2CD6	ENST00000286195.7	TSL:1	c.1582-3395G>T		intron	N/A	ENSP00000286195.3	Q53TS8-1
	C2CD6	ENST00000957096.1		c.4621G>T	p.Ala1541Ser	missense	Exon 12 of 13	ENSP00000627155.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.0020
DANN	Benign	0.95
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.99	T
PhyloP100		-1.9
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.64	N
REVEL	Benign	0.0030
Sift	Benign	0.90	T
Sift4G	Benign	0.69	T
Vest4		0.043
MutPred		0.28		Gain of relative solvent accessibility (P = 0.0027)
MVP		0.048
MPC		0.13
ClinPred		0.061	T
GERP RS		-1.6
gMVP		0.0054
Mutation Taster		=99/1	polymorphism

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: rs200411331; hg19: chr2-202356020;