chr17-20580332-C-T

Variant names:

• chr17-20580332-C-T
• rs1259372423
• NM_001190790.2:c.449C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001190790.2(CDRT15L2):​c.449C>T​(p.Ala150Val) 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. 16/22 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: -0.106
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06968284).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190790.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDRT15L2	NM_001190790.2	MANE Select	c.449C>T	p.Ala150Val	missense	Exon 2 of 2	NP_001177719.1	A8MXV6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDRT15L2	ENST00000399044.1	TSL:2 MANE Select	c.449C>T	p.Ala150Val	missense	Exon 2 of 2	ENSP00000382000.1	A8MXV6
	CDRT15L2	ENST00000661883.1		c.414+35C>T		intron	N/A	ENSP00000499342.1	A0A590UJC2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.9
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0010	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.11
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.013
Sift	Benign	0.16	T
Sift4G	Pathogenic	0.0	D
Vest4		0.13
MutPred		0.31		Gain of catalytic residue at A150 (P = 0.0028)
MVP		0.067
MPC		0.34
ClinPred		0.21	T
GERP RS		0.12
Varity_R		0.043
gMVP		0.027
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1259372423; hg19: chr17-20483645;