Variant X-150777473-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_031462.4(CD99L2):c.506G>A(p.Arg169Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000785 in 1,209,673 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., 3 hem., cov: 24)

Exomes 𝑓: 0.000077 ( 0 hom. 34 hem. )

Consequence

CD99L2
NM_031462.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.300

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01769784).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD99L2	NM_031462.4 linkuse as main transcript	c.506G>A	p.Arg169Gln	missense_variant	8/11	ENST00000370377.8	NP_113650.2	Q8TCZ2-1A0A024RC16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD99L2	ENST00000370377.8 linkuse as main transcript	c.506G>A	p.Arg169Gln	missense_variant	8/11	1	NM_031462.4	ENSP00000359403.3		Q8TCZ2-1

Frequencies

GnomAD3 genomes

AF:

0.0000978

AC:

AN:

112478

Hom.:

Cov.:

AF XY:

0.0000866

AC XY:

AN XY:

34644

show subpopulations

Gnomad AFR

AF:

0.000162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000377

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000367

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000751

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000121

AC:

AN:

181412

Hom.:

AF XY:

0.000136

AC XY:

AN XY:

65998

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.000187

Gnomad ASJ exome

AF:

0.000809

Gnomad EAS exome

AF:

0.000146

Gnomad SAS exome

AF:

0.000159

Gnomad FIN exome

AF:

0.0000640

Gnomad NFE exome

AF:

0.0000368

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000766

AC:

AN:

1097145

Hom.:

Cov.:

AF XY:

0.0000938

AC XY:

AN XY:

362543

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.000229

Gnomad4 ASJ exome

AF:

0.000776

Gnomad4 EAS exome

AF:

0.000199

Gnomad4 SAS exome

AF:

0.0000926

Gnomad4 FIN exome

AF:

0.0000743

Gnomad4 NFE exome

AF:

0.0000475

Gnomad4 OTH exome

AF:

0.0000869

GnomAD4 genome

AF:

0.0000978

AC:

AN:

112528

Hom.:

Cov.:

AF XY:

0.0000864

AC XY:

AN XY:

34704

show subpopulations

Gnomad4 AFR

AF:

0.000161

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000377

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000368

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000751

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000304

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000173

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

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

Nov 03, 2022

The c.518G>A (p.R173Q) alteration is located in exon 8 (coding exon 8) of the CD99L2 gene. This alteration results from a G to A substitution at nucleotide position 518, causing the arginine (R) at amino acid position 173 to be replaced by a glutamine (Q). 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

0.083

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.6

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

T;.;.;.;.

FATHMM_MKL

Benign

0.0067

LIST_S2

Benign

0.77

T;T;T;T;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.018

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;.;.;.;.

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.63

N;.;N;N;N

REVEL

Benign

0.015

Sift

Benign

0.42

T;.;T;T;T

Sift4G

Benign

0.37

T;T;T;T;T

Polyphen

0.14

B;.;.;B;B

Vest4

0.051

MVP

0.36

MPC

0.085

ClinPred

0.012

GERP RS

-2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.031

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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