chr17-20580287-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001190790.2(CDRT15L2):​c.404C>T​(p.Pro135Leu) 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. 14/21 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

CDRT15L2
NM_001190790.2 missense

Scores

3
1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.958
Variant links:
Genes affected
CDRT15L2 (HGNC:34075): (CMT1A duplicated region transcript 15 like 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13394323).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDRT15L2NM_001190790.2 linkc.404C>T p.Pro135Leu missense_variant Exon 2 of 2 ENST00000399044.1 NP_001177719.1 A8MXV6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDRT15L2ENST00000399044.1 linkc.404C>T p.Pro135Leu missense_variant Exon 2 of 2 2 NM_001190790.2 ENSP00000382000.1 A8MXV6
CDRT15L2ENST00000661883.1 linkc.404C>T p.Pro135Leu missense_variant Exon 2 of 3 ENSP00000499342.1 A0A590UJC2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.404C>T (p.P135L) alteration is located in exon 2 (coding exon 2) of the CDRT15L2 gene. This alteration results from a C to T substitution at nucleotide position 404, causing the proline (P) at amino acid position 135 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
16
DANN
Benign
0.97
DEOGEN2
Benign
0.11
T
Eigen
Benign
-0.79
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.0045
N
LIST_S2
Benign
0.53
T
M_CAP
Benign
0.0064
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
0.55
N
PrimateAI
Uncertain
0.50
T
PROVEAN
Pathogenic
-4.8
D
REVEL
Benign
0.064
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Vest4
0.24
MutPred
0.21
Gain of helix (P = 0.0082);
MVP
0.099
MPC
1.1
ClinPred
0.75
D
GERP RS
-1.3
Varity_R
0.098
gMVP
0.050

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2043285567; hg19: chr17-20483600; API