X-150777473-C-T

Variant names:

• chrX-150777473-C-T
• rs143706982
• NM_031462.4:c.506G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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. 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. R169W) has been classified 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.300
• Publications: 2 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
CD99L2	NM_031462.4	c.506G>A	p.Arg169Gln	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.506G>A	p.Arg169Gln	missense_variant	Exon 8 of 11	1	NM_031462.4	ENSP00000359403.3

Frequencies

GnomAD3 genomes AF: 0.0000978 AC: 11 AN: 112478 Hom.: 0 Cov.: 24

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

GnomAD2 exomes AF: 0.000121 AC: 22 AN: 181412 AF XY: 0.000136

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 FIN exome AF: 0.0000640

Gnomad NFE exome AF: 0.0000368

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000766 AC: 84 AN: 1097145 Hom.: 0 Cov.: 30 AF XY: 0.0000938 AC XY: 34 AN XY: 362543

African (AFR) AF: 0.0000380 AC: 1 AN: 26349

American (AMR) AF: 0.000229 AC: 8 AN: 34948

Ashkenazi Jewish (ASJ) AF: 0.000776 AC: 15 AN: 19340

East Asian (EAS) AF: 0.000199 AC: 6 AN: 30192

South Asian (SAS) AF: 0.0000926 AC: 5 AN: 53976

European-Finnish (FIN) AF: 0.0000743 AC: 3 AN: 40370

Middle Eastern (MID) AF: 0.000485 AC: 2 AN: 4127

European-Non Finnish (NFE) AF: 0.0000475 AC: 40 AN: 841789

Other (OTH) AF: 0.0000869 AC: 4 AN: 46054

GnomAD4 genome AF: 0.0000978 AC: 11 AN: 112528 Hom.: 0 Cov.: 24 AF XY: 0.0000864 AC XY: 3 AN XY: 34704

African (AFR) AF: 0.000161 AC: 5 AN: 31003

American (AMR) AF: 0.00 AC: 0 AN: 10733

Ashkenazi Jewish (ASJ) AF: 0.000377 AC: 1 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3570

South Asian (SAS) AF: 0.000368 AC: 1 AN: 2714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6161

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0000751 AC: 4 AN: 53259

Other (OTH) AF: 0.00 AC: 0 AN: 1533

Alfa AF: 0.000304 Hom.: 1

Bravo AF: 0.000110

ESP6500AA AF: 0.000522 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000173 AC: 21

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.6
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T;.;.;.;.
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.77	T;T;T;T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.018	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;.;.;.;.
PhyloP100		-0.30
PrimateAI	Benign	0.19	T
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	T
GERP RS		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.11
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs143706982; hg19: chrX-149945946; COSMIC: COSV105253432;