Variant X-150776287-A-G 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.542T>C(p.Val181Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000183 in 1,204,215 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 5 hem., cov: 23)

Exomes 𝑓: 0.0000092 ( 0 hom. 3 hem. )

Consequence

CD99L2
NM_031462.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.970

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=0.07212618).

BS2

High Hemizygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD99L2	NM_031462.4 linkuse as main transcript	c.542T>C	p.Val181Ala	missense_variant	9/11	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.542T>C	p.Val181Ala	missense_variant	9/11	1	NM_031462.4	ENSP00000359403.3		Q8TCZ2-1

Frequencies

GnomAD3 genomes

AF:

0.000107

AC:

AN:

112223

Hom.:

Cov.:

AF XY:

0.000145

AC XY:

AN XY:

34395

show subpopulations

Gnomad AFR

AF:

0.000357

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000933

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000179

AC:

AN:

167373

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

54183

show subpopulations

Gnomad AFR exome

AF:

0.0000808

Gnomad AMR exome

AF:

0.0000393

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000136

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000916

AC:

AN:

1091992

Hom.:

Cov.:

AF XY:

0.00000838

AC XY:

AN XY:

357942

show subpopulations

Gnomad4 AFR exome

AF:

0.000305

Gnomad4 AMR exome

AF:

0.0000292

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000107

AC:

AN:

112223

Hom.:

Cov.:

AF XY:

0.000145

AC XY:

AN XY:

34395

show subpopulations

Gnomad4 AFR

AF:

0.000357

Gnomad4 AMR

AF:

0.0000933

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000117

ExAC

AF:

0.0000165

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

Nov 09, 2024

The c.554T>C (p.V185A) alteration is located in exon 9 (coding exon 9) of the CD99L2 gene. This alteration results from a T to C substitution at nucleotide position 554, causing the valine (V) at amino acid position 185 to be replaced by an alanine (A). 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

0.088

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.91

CADD

Benign

DANN

Benign

0.38

DEOGEN2

Benign

0.016

T;.;.;.;.

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.62

T;T;T;T;T

M_CAP

Benign

0.0092

MetaRNN

Benign

0.072

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.75

N;.;.;.;.

PrimateAI

Benign

0.34

PROVEAN

Benign

0.14

N;.;N;N;N

REVEL

Benign

0.011

Sift

Benign

0.48

T;.;T;T;T

Sift4G

Benign

0.20

T;T;T;T;T

Polyphen

0.27

B;.;.;B;B

Vest4

0.21

MutPred

0.21

Loss of sheet (P = 0.0084);.;.;.;.;

MVP

0.31

MPC

0.11

ClinPred

0.67

GERP RS

0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.035

gMVP

0.093

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