Variant X-150769059-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_031462.4(CD99L2):c.764C>T(p.Pro255Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000111 in 1,156,810 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 37 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., 7 hem., cov: 24)

Exomes 𝑓: 0.000097 ( 0 hom. 30 hem. )

Consequence

CD99L2
NM_031462.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.438

Variant links:

Genes affected

CD99L2 (HGNC:18237): (CD99 molecule like 2) This gene encodes a cell-surface protein that is similar to CD99. A similar protein in mouse functions as an adhesion molecule during leukocyte extravasation. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

CD99L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.091511935).

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD99L2	NM_031462.4 link	c.764C>T	p.Pro255Leu	missense_variant	11/11	ENST00000370377.8	NP_113650.2	Q8TCZ2-1A0A024RC16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD99L2	ENST00000370377.8 link	c.764C>T	p.Pro255Leu	missense_variant	11/11	1	NM_031462.4	ENSP00000359403.3		Q8TCZ2-1

Frequencies

GnomAD3 genomes

AF:

0.000239

AC:

AN:

112784

Hom.:

Cov.:

AF XY:

0.000200

AC XY:

AN XY:

34934

show subpopulations

Gnomad AFR

AF:

0.0000322

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000488

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000615

AC:

AN:

130027

Hom.:

AF XY:

0.0000229

AC XY:

AN XY:

43735

show subpopulations

Gnomad AFR exome

AF:

0.000204

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:

0.0000730

Gnomad NFE exome

AF:

0.0000779

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000967

AC:

101

AN:

1044026

Hom.:

Cov.:

AF XY:

0.0000881

AC XY:

AN XY:

340622

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:

0.0000865

Gnomad4 FIN exome

AF:

0.0000772

Gnomad4 NFE exome

AF:

0.000109

Gnomad4 OTH exome

AF:

0.0000912

GnomAD4 genome

AF:

0.000239

AC:

AN:

112784

Hom.:

Cov.:

AF XY:

0.000200

AC XY:

AN XY:

34934

show subpopulations

Gnomad4 AFR

AF:

0.0000322

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000488

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00130

Hom.:

Bravo

AF:

0.000110

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2024

The c.794C>T (p.P265L) alteration is located in exon 12 (coding exon 12) of the CD99L2 gene. This alteration results from a C to T substitution at nucleotide position 794, causing the proline (P) at amino acid position 265 to be replaced by a leucine (L). 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

0.092

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

T;.;.;.;.

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.58

T;T;T;T;T

M_CAP

Benign

0.0089

MetaRNN

Benign

0.092

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.3

L;.;.;.;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.26

N;.;N;N;N

REVEL

Benign

0.056

Sift

Uncertain

0.0080

D;.;D;D;D

Sift4G

Uncertain

0.0070

D;D;D;D;D

Polyphen

0.98

D;.;.;D;D

Vest4

0.31

MVP

0.14

MPC

0.095

ClinPred

0.054

GERP RS

0.63

Varity_R

0.091

gMVP

0.32

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