Genetic Variant CDRT15L2:p.Ala100Val (chr17-20580182-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001190790.2(CDRT15L2):c.299C>T(p.Ala100Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00043 in 1,477,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

CDRT15L2
NM_001190790.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.705

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018744439).

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.299C>T	p.Ala100Val	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.299C>T	p.Ala100Val	missense	Exon 2 of 2	ENSP00000382000.1	A8MXV6
	CDRT15L2	ENST00000661883.1		c.299C>T	p.Ala100Val	missense	Exon 2 of 3	ENSP00000499342.1	A0A590UJC2

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000537

AC:

AN:

100594

AF XY:

0.000509

show subpopulations

Gnomad AFR exome

AF:

0.000918

Gnomad AMR exome

AF:

0.000381

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00104

Gnomad FIN exome

AF:

0.0000745

Gnomad NFE exome

AF:

0.000787

Gnomad OTH exome

AF:

0.000357

GnomAD4 exome

AF:

0.000423

AC:

561

AN:

1325368

Hom.:

Cov.:

AF XY:

0.000406

AC XY:

262

AN XY:

645930

show subpopulations

African (AFR)

AF:

0.000856

AC:

AN:

29208

American (AMR)

AF:

0.000458

AC:

AN:

24038

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20026

East Asian (EAS)

AF:

0.000227

AC:

AN:

35200

South Asian (SAS)

AF:

0.0000454

AC:

AN:

66126

European-Finnish (FIN)

AF:

0.000131

AC:

AN:

45970

Middle Eastern (MID)

AF:

0.000188

AC:

AN:

5310

European-Non Finnish (NFE)

AF:

0.000463

AC:

484

AN:

1044770

Other (OTH)

AF:

0.000420

AC:

AN:

54720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

103

137

171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000486

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.000770

AC:

AN:

41540

American (AMR)

AF:

0.000392

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5162

South Asian (SAS)

AF:

0.000209

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000470

AC:

AN:

68018

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000144

Hom.:

Bravo

AF:

0.000416

ExAC

AF:

0.000262

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.018

Eigen

Benign

-0.84

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0064

LIST_S2

Benign

0.51

M_CAP

Benign

0.0033

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

0.70

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.93

REVEL

Benign

0.020

Sift

Benign

0.036

Sift4G

Uncertain

0.032

Vest4

0.062

MVP

0.092

MPC

0.52

ClinPred

0.014

GERP RS

0.38

PromoterAI

-0.016

Neutral

(source)

Varity_R

0.052

gMVP

0.017

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over