X-150776285-C-A

Variant names:

• chrX-150776285-C-A
• NM_031462.4:c.544G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031462.4(CD99L2):​c.544G>T​(p.Ala182Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: CD99L2 NM_031462.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.75
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24863079).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD99L2	NM_031462.4	c.544G>T	p.Ala182Ser	missense_variant	Exon 9 of 11	ENST00000370377.8	NP_113650.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD99L2	ENST00000370377.8	c.544G>T	p.Ala182Ser	missense_variant	Exon 9 of 11	1	NM_031462.4	ENSP00000359403.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.556G>T (p.A186S) alteration is located in exon 9 (coding exon 9) of the CD99L2 gene. This alteration results from a G to T substitution at nucleotide position 556, causing the alanine (A) at amino acid position 186 to be replaced by a serine (S). 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	0.11
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.;.;.;.
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.87	D;D;D;D;D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.25	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;.;.;.;.
PhyloP100		1.8
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.83	N;.;N;N;N
REVEL	Benign	0.073
Sift	Uncertain	0.011	D;.;D;D;D
Sift4G	Uncertain	0.016	D;D;T;D;D
Polyphen		0.67	P;.;.;P;B
Vest4		0.32
MutPred		0.22		Gain of glycosylation at A182 (P = 0.0154);.;.;.;.;
MVP		0.38
MPC		0.32
ClinPred		0.77	D
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.18
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

hg19: chrX-149944758;