chr2-201491612-T-C

Variant names:

• chr2-201491612-T-C
• NM_001168221.2:c.4729A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001168221.2(CATSPERT):​c.4729A>G​(p.Ser1577Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CATSPERT NM_001168221.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.326
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07112926).

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.4729A>G	p.Ser1577Gly	missense	Exon 15 of 16	NP_001161693.1	Q53TS8-4
	CATSPERT	NM_152525.6		c.1582-3710A>G		intron	N/A	NP_689738.3
	CATSPERT	NM_001168216.2		c.*50-3710A>G		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.4729A>G	p.Ser1577Gly	missense	Exon 15 of 16	ENSP00000409937.1	Q53TS8-4
	C2CD6	ENST00000286195.7	TSL:1	c.1582-3710A>G		intron	N/A	ENSP00000286195.3	Q53TS8-1
	C2CD6	ENST00000957096.1		c.4306A>G	p.Ser1436Gly	missense	Exon 12 of 13	ENSP00000627155.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.9
DANN	Benign	0.92
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.33
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.026
Sift	Benign	0.045	D
Sift4G	Benign	0.54	T
Vest4		0.11
MutPred		0.18		Gain of sheet (P = 0.0477)
MVP		0.067
MPC		0.15
ClinPred		0.13	T
GERP RS		0.82
gMVP		0.0099
Mutation Taster		=100/0	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

hg19: chr2-202356335;