17-20580236-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001190790.2(CDRT15L2):​c.353C>A​(p.Ala118Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000679 in 1,472,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000038 ( 0 hom. )

Consequence

CDRT15L2
NM_001190790.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.835
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.022723377).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDRT15L2NM_001190790.2 linkc.353C>A p.Ala118Glu 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.353C>A p.Ala118Glu missense_variant Exon 2 of 2 2 NM_001190790.2 ENSP00000382000.1 A8MXV6
CDRT15L2ENST00000661883.1 linkc.353C>A p.Ala118Glu missense_variant Exon 2 of 3 ENSP00000499342.1 A0A590UJC2

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
151934
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000605
AC:
5
AN:
82664
Hom.:
0
AF XY:
0.0000243
AC XY:
1
AN XY:
41098
show subpopulations
Gnomad AFR exome
AF:
0.000810
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000379
AC:
5
AN:
1320544
Hom.:
0
Cov.:
31
AF XY:
0.00000311
AC XY:
2
AN XY:
643786
show subpopulations
Gnomad4 AFR exome
AF:
0.000173
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152050
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000604
ExAC
AF:
0.0000340
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 07, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.353C>A (p.A118E) alteration is located in exon 2 (coding exon 2) of the CDRT15L2 gene. This alteration results from a C to A substitution at nucleotide position 353, causing the alanine (A) at amino acid position 118 to be replaced by a glutamic acid (E). 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
0.21
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
6.5
DANN
Benign
0.93
DEOGEN2
Benign
0.14
T
Eigen
Benign
-0.87
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0023
N
LIST_S2
Benign
0.42
T
M_CAP
Benign
0.0062
T
MetaRNN
Benign
0.023
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.0
N
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.094
Sift
Uncertain
0.013
D
Sift4G
Uncertain
0.026
D
Vest4
0.082
MutPred
0.088
Gain of solvent accessibility (P = 0.0411);
MVP
0.17
MPC
0.64
ClinPred
0.055
T
GERP RS
-1.2
Varity_R
0.19
gMVP
0.025

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: rs548860276; hg19: chr17-20483549; API