17-20580267-C-A

Variant names:

• chr17-20580267-C-A
• NM_001190790.2:c.384C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001190790.2(CDRT15L2):​c.384C>A​(p.Asp128Glu) 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03

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]

ACMG classification

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=0.090875715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDRT15L2	NM_001190790.2	c.384C>A	p.Asp128Glu	missense_variant	Exon 2 of 2	ENST00000399044.1	NP_001177719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDRT15L2	ENST00000399044.1	c.384C>A	p.Asp128Glu	missense_variant	Exon 2 of 2	2	NM_001190790.2	ENSP00000382000.1
CDRT15L2	ENST00000661883.1	c.384C>A	p.Asp128Glu	missense_variant	Exon 2 of 3			ENSP00000499342.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.384C>A (p.D128E) 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 384, causing the aspartic acid (D) at amino acid position 128 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	Uncertain	0.36
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.9
DANN	Benign	0.83
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.34	N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.084
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.056	T
Vest4		0.19
MutPred		0.10		Gain of helix (P = 0.062);
MVP		0.15
MPC		0.73
ClinPred		0.19	T
GERP RS		0.45
Varity_R		0.14
gMVP		0.0059

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-20483580;