17-20579954-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001190790.2(CDRT15L2):​c.211C>T​(p.His71Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000042 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CDRT15L2
NM_001190790.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.924
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.

BP4
Computational evidence support a benign effect (MetaRNN=0.12618041).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDRT15L2NM_001190790.2 linkc.211C>T p.His71Tyr missense_variant Exon 1 of 2 ENST00000399044.1 NP_001177719.1 A8MXV6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDRT15L2ENST00000399044.1 linkc.211C>T p.His71Tyr missense_variant Exon 1 of 2 2 NM_001190790.2 ENSP00000382000.1 A8MXV6
CDRT15L2ENST00000661883.1 linkc.211C>T p.His71Tyr missense_variant Exon 1 of 3 ENSP00000499342.1 A0A590UJC2

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
1
AN:
151276
Hom.:
0
Cov.:
32
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000196
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:
0.00000518
AC:
1
AN:
192922
Hom.:
0
AF XY:
0.00000966
AC XY:
1
AN XY:
103502
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000123
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000420
AC:
6
AN:
1428558
Hom.:
0
Cov.:
31
AF XY:
0.00000424
AC XY:
3
AN XY:
707462
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.00000457
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000661
AC:
1
AN:
151392
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
73982
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000196
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000169
Hom.:
0

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 19, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.211C>T (p.H71Y) alteration is located in exon 1 (coding exon 1) of the CDRT15L2 gene. This alteration results from a C to T substitution at nucleotide position 211, causing the histidine (H) at amino acid position 71 to be replaced by a tyrosine (Y). 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
0.14
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
2.3
DANN
Benign
0.90
DEOGEN2
Benign
0.030
T
Eigen
Benign
-0.73
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.0057
N
LIST_S2
Benign
0.47
T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.55
N
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.081
Sift
Benign
0.048
D
Sift4G
Benign
0.64
T
Vest4
0.23
MutPred
0.55
Loss of disorder (P = 0.0488);
MVP
0.14
MPC
0.53
ClinPred
0.060
T
GERP RS
0.64
Varity_R
0.079
gMVP
0.075

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: rs1254331447; hg19: chr17-20483267; API