X-150898541-C-A

Variant names:

• chrX-150898541-C-A
• NM_031462.4:c.48G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031462.4(CD99L2):​c.48G>T​(p.Leu16Phe) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: CD99L2 NM_031462.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.50

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37236196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD99L2	NM_031462.4	c.48G>T	p.Leu16Phe	missense_variant	Exon 1 of 11	ENST00000370377.8	NP_113650.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD99L2	ENST00000370377.8	c.48G>T	p.Leu16Phe	missense_variant	Exon 1 of 11	1	NM_031462.4	ENSP00000359403.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1000520 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 320262

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.48G>T (p.L16F) alteration is located in exon 1 (coding exon 1) of the CD99L2 gene. This alteration results from a G to T substitution at nucleotide position 48, causing the leucine (L) at amino acid position 16 to be replaced by a phenylalanine (F). 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	0.095
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.073	T;.;.;.;.
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.83	T;T;T;T;T
M_CAP	Pathogenic	0.66	D
MetaRNN	Benign	0.37	T;T;T;T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.9	L;L;L;L;L
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.7	N;.;N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.014	D;.;D;D;D
Sift4G	Benign	0.17	T;T;T;T;T
Polyphen		1.0	D;.;.;D;D
Vest4		0.30
MutPred		0.29		Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);
MVP		0.84
MPC		0.080
ClinPred		0.73	D
GERP RS		4.0
Varity_R		0.31
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-150067014;