NM_031462.4:c.604G>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.604G>A(p.Val202Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000367 in 1,209,951 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 148 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.00041 ( 0 hom., 16 hem., cov: 23)

Exomes 𝑓: 0.00036 ( 0 hom. 132 hem. )

Consequence

CD99L2
NM_031462.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.38

Publications

3 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=0.058446467).

BP6

Variant X-150776225-C-T is Benign according to our data. Variant chrX-150776225-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2372869.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS2

High Hemizygotes in GnomAd4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD99L2	NM_031462.4 link	c.604G>A	p.Val202Ile	missense_variant	Exon 9 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.604G>A	p.Val202Ile	missense_variant	Exon 9 of 11	1	NM_031462.4	ENSP00000359403.3		Q8TCZ2-1

Frequencies

GnomAD3 genomes

AF:

0.000410

AC:

AN:

112264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000875

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000186

Gnomad ASJ

AF:

0.000754

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000282

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000280

AC:

AN:

182291

AF XY:

0.000254

show subpopulations

Gnomad AFR exome

AF:

0.000915

Gnomad AMR exome

AF:

0.000184

Gnomad ASJ exome

AF:

0.000537

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000344

Gnomad OTH exome

AF:

0.000447

GnomAD4 exome

AF:

0.000363

AC:

398

AN:

1097687

Hom.:

Cov.:

AF XY:

0.000364

AC XY:

132

AN XY:

363079

show subpopulations

African (AFR)

AF:

0.00106

AC:

AN:

26389

American (AMR)

AF:

0.000199

AC:

AN:

35176

Ashkenazi Jewish (ASJ)

AF:

0.000774

AC:

AN:

19371

East Asian (EAS)

AF:

0.00

AC:

AN:

30174

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54091

European-Finnish (FIN)

AF:

0.0000247

AC:

AN:

40478

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4131

European-Non Finnish (NFE)

AF:

0.000397

AC:

334

AN:

841807

Other (OTH)

AF:

0.000260

AC:

AN:

46070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000410

AC:

AN:

112264

Hom.:

Cov.:

AF XY:

0.000465

AC XY:

AN XY:

34438

show subpopulations

African (AFR)

AF:

0.000875

AC:

AN:

30863

American (AMR)

AF:

0.000186

AC:

AN:

10742

Ashkenazi Jewish (ASJ)

AF:

0.000754

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3534

South Asian (SAS)

AF:

0.00

AC:

AN:

2707

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6145

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.000282

AC:

AN:

53178

Other (OTH)

AF:

0.00

AC:

AN:

1521

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000345

Hom.:

Bravo

AF:

0.000438

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00104

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000321

AC:

EpiCase

AF:

0.000328

EpiControl

AF:

0.000655

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

Oct 25, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.616G>A (p.V206I) alteration is located in exon 9 (coding exon 9) of the CD99L2 gene. This alteration results from a G to A substitution at nucleotide position 616, causing the valine (V) at amino acid position 206 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CD99L2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

T;.;.;.;.

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.89

D;D;D;D;D

M_CAP

Benign

0.063

MetaRNN

Benign

0.058

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;.;.;.;.

PhyloP100

3.4

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.62

N;.;N;N;N

REVEL

Benign

0.075

Sift

Benign

0.043

D;.;D;T;T

Sift4G

Benign

0.092

T;T;T;T;T

Polyphen

1.0

D;.;.;D;D

Vest4

0.20

MVP

0.49

MPC

0.36

ClinPred

0.047

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.098

gMVP

0.41

Mutation Taster

=98/2

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.604G>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