NM_031462.4:c.782G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_031462.4(CD99L2):c.782G>A(p.Arg261Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000765 in 1,149,669 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 34 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., 2 hem., cov: 25)

Exomes 𝑓: 0.000076 ( 0 hom. 32 hem. )

Consequence

CD99L2
NM_031462.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.608

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021325022).

BP6

Variant X-150769041-C-T is Benign according to our data. Variant chrX-150769041-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 764770.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD99L2	NM_031462.4 link	c.782G>A	p.Arg261Gln	missense_variant	Exon 11 of 11	ENST00000370377.8	NP_113650.2	Q8TCZ2-1A0A024RC16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD99L2	ENST00000370377.8 link	c.782G>A	p.Arg261Gln	missense_variant	Exon 11 of 11	1	NM_031462.4	ENSP00000359403.3		Q8TCZ2-1

Frequencies

GnomAD3 genomes

AF:

0.0000887

AC:

AN:

112694

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000161

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000186

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00108

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000964

AC:

AN:

124521

AF XY:

0.000120

show subpopulations

Gnomad AFR exome

AF:

0.000210

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000160

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000762

AC:

AN:

1036922

Hom.:

Cov.:

AF XY:

0.0000949

AC XY:

AN XY:

337180

show subpopulations

African (AFR)

AF:

0.0000910

AC:

AN:

21983

American (AMR)

AF:

0.00

AC:

AN:

20220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17272

East Asian (EAS)

AF:

0.0000382

AC:

AN:

26167

South Asian (SAS)

AF:

0.000814

AC:

AN:

45427

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37886

Middle Eastern (MID)

AF:

0.000258

AC:

AN:

3879

European-Non Finnish (NFE)

AF:

0.0000439

AC:

AN:

820549

Other (OTH)

AF:

0.0000459

AC:

AN:

43539

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000798

AC:

AN:

112747

Hom.:

Cov.:

AF XY:

0.0000573

AC XY:

AN XY:

34899

show subpopulations

African (AFR)

AF:

0.000161

AC:

AN:

31089

American (AMR)

AF:

0.000186

AC:

AN:

10751

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3561

South Asian (SAS)

AF:

0.000725

AC:

AN:

2759

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6207

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53289

Other (OTH)

AF:

0.00

AC:

AN:

1540

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000136

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 27, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.812G>A (p.R271Q) alteration is located in exon 12 (coding exon 12) of the CD99L2 gene. This alteration results from a G to A substitution at nucleotide position 812, causing the arginine (R) at amino acid position 271 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Aug 11, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.021

T;.;.;.;.

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.59

T;T;T;T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.021

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.;.;.;.

PhyloP100

0.61

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.3

N;.;N;N;N

REVEL

Benign

0.039

Sift

Benign

0.24

T;.;T;T;T

Sift4G

Benign

0.26

T;T;T;T;T

Polyphen

0.0010

B;.;.;B;B

Vest4

0.10

MVP

0.73

MPC

0.27

ClinPred

0.082

GERP RS

0.64

Varity_R

0.051

gMVP

0.24

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

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NM_031462.4:c.782G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over