Genetic Variant CDRT15L2:p.His71Tyr (chr17-20579954-C-T) – ACMG Classification: Likely_benign (-2 pts)

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

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]

CDRT15L2 links:

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
CDRT15L2	NM_001190790.2 link	c.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
CDRT15L2	ENST00000399044.1 link	c.211C>T	p.His71Tyr	missense_variant	Exon 1 of 2	2	NM_001190790.2	ENSP00000382000.1		A8MXV6
CDRT15L2	ENST00000661883.1 link	c.211C>T	p.His71Tyr	missense_variant	Exon 1 of 3			ENSP00000499342.1		A0A590UJC2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151276

Hom.:

Cov.:

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:

AN:

192922

Hom.:

AF XY:

0.00000966

AC XY:

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:

AN:

1428558

Hom.:

Cov.:

AF XY:

0.00000424

AC XY:

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:

AN:

151392

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

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.:

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

BayesDel_noAF

Benign

-0.57

CADD

Benign

2.3

DANN

Benign

0.90

DEOGEN2

Benign

0.030

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.47

M_CAP

Benign

0.010

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.2

REVEL

Benign

0.081

Sift

Benign

0.048

Sift4G

Benign

0.64

Vest4

0.23

MutPred

0.55

Loss of disorder (P = 0.0488);

MVP

0.14

MPC

0.53

ClinPred

0.060

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over