chr2-201492326-T-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong
The NM_001168221.2(C2CD6):c.4015A>G(p.Met1339Val) 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. 13/18 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
C2CD6
NM_001168221.2 missense
NM_001168221.2 missense
Scores
16
Clinical Significance
Conservation
PhyloP100: 0.0200
Genes affected
C2CD6 (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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, C2CD6
BP4
?
Computational evidence support a benign effect (MetaRNN=0.058572978).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
C2CD6 | NM_001168221.2 | c.4015A>G | p.Met1339Val | missense_variant | 15/16 | ENST00000439140.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C2CD6 | ENST00000439140.6 | c.4015A>G | p.Met1339Val | missense_variant | 15/16 | 1 | NM_001168221.2 | A2 | |
C2CD6 | ENST00000286195.7 | c.1581+3569A>G | intron_variant | 1 | P2 | ||||
C2CD6 | ENST00000439802.5 | c.*49+3569A>G | intron_variant | 2 | |||||
C2CD6 | ENST00000482942.1 | n.101-4424A>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 03, 2022 | The c.4015A>G (p.M1339V) alteration is located in exon 15 (coding exon 15) of the ALS2CR11 gene. This alteration results from a A to G substitution at nucleotide position 4015, causing the methionine (M) at amino acid position 1339 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Vest4
MutPred
Loss of ubiquitination at K1341 (P = 0.0724);
MVP
MPC
ClinPred
T
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.