rs781890633

Variant names:

• chrX-150777474-G-A
• rs781890633
• NM_031462.4:c.505C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_031462.4(CD99L2):​c.505C>T​(p.Arg169Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000215 in 1,209,598 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R169Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 3 hem., cov: 23)
  • Exomes 𝑓: 0.000021 (0 hom. 11 hem.)
• Consequence: CD99L2 NM_031462.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.925
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0930706).
• BS2: High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD99L2	NM_031462.4	c.505C>T	p.Arg169Trp	missense_variant	Exon 8 of 11	ENST00000370377.8	NP_113650.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD99L2	ENST00000370377.8	c.505C>T	p.Arg169Trp	missense_variant	Exon 8 of 11	1	NM_031462.4	ENSP00000359403.3

Frequencies

GnomAD3 genomes AF: 0.0000267 AC: 3 AN: 112408 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000647

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000221 AC: 4 AN: 181402 AF XY: 0.0000303

Gnomad AFR exome AF: 0.0000762

Gnomad AMR exome AF: 0.0000373

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000210 AC: 23 AN: 1097140 Hom.: 0 Cov.: 30 AF XY: 0.0000303 AC XY: 11 AN XY: 362536

African (AFR) AF: 0.0000759 AC: 2 AN: 26347

American (AMR) AF: 0.0000572 AC: 2 AN: 34940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19346

East Asian (EAS) AF: 0.00 AC: 0 AN: 30186

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 53976

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40367

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.0000202 AC: 17 AN: 841794

Other (OTH) AF: 0.0000217 AC: 1 AN: 46053

GnomAD4 genome AF: 0.0000267 AC: 3 AN: 112458 Hom.: 0 Cov.: 23 AF XY: 0.0000866 AC XY: 3 AN XY: 34648

African (AFR) AF: 0.0000646 AC: 2 AN: 30962

American (AMR) AF: 0.00 AC: 0 AN: 10730

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2655

East Asian (EAS) AF: 0.00 AC: 0 AN: 3561

South Asian (SAS) AF: 0.00 AC: 0 AN: 2722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6154

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53236

Other (OTH) AF: 0.00 AC: 0 AN: 1535

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.517C>T (p.R173W) alteration is located in exon 8 (coding exon 8) of the CD99L2 gene. This alteration results from a C to T substitution at nucleotide position 517, causing the arginine (R) at amino acid position 173 to be replaced by a tryptophan (W). 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	0.13
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	T;.;.;.;.
FATHMM_MKL	Benign	0.010	N
LIST_S2	Uncertain	0.93	D;D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.093	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.;.;.;.
PhyloP100		-0.93
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.6	N;.;N;N;N
REVEL	Benign	0.059
Sift	Uncertain	0.025	D;.;D;D;D
Sift4G	Uncertain	0.022	D;D;D;D;D
Polyphen		1.0	D;.;.;D;D
Vest4		0.17
MVP		0.27
MPC		0.36
ClinPred		0.52	D
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.062
gMVP		0.16
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs781890633; hg19: chrX-149945947; COSMIC: COSV105253395;