X-150769059-G-A

Variant names:

• chrX-150769059-G-A
• rs782752007
• NM_031462.4:c.764C>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.764C>T​(p.Pro255Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000111 in 1,156,810 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., 7 hem., cov: 24)
  • Exomes 𝑓: 0.000097 (0 hom. 30 hem.)
• Consequence: CD99L2 NM_031462.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.438
• Publications: 4 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=0.091511935).
• BS2: High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD99L2	NM_031462.4	c.764C>T	p.Pro255Leu	missense_variant	Exon 11 of 11	ENST00000370377.8	NP_113650.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD99L2	ENST00000370377.8	c.764C>T	p.Pro255Leu	missense_variant	Exon 11 of 11	1	NM_031462.4	ENSP00000359403.3

Frequencies

GnomAD3 genomes AF: 0.000239 AC: 27 AN: 112784 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000322

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: 0.000488

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000615 AC: 8 AN: 130027 AF XY: 0.0000229

Gnomad AFR exome AF: 0.000204

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000730

Gnomad NFE exome AF: 0.0000779

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000967 AC: 101 AN: 1044026 Hom.: 0 Cov.: 31 AF XY: 0.0000881 AC XY: 30 AN XY: 340622

African (AFR) AF: 0.00 AC: 0 AN: 22301

American (AMR) AF: 0.00 AC: 0 AN: 21418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17518

East Asian (EAS) AF: 0.00 AC: 0 AN: 26560

South Asian (SAS) AF: 0.0000865 AC: 4 AN: 46251

European-Finnish (FIN) AF: 0.0000772 AC: 3 AN: 38882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3913

European-Non Finnish (NFE) AF: 0.000109 AC: 90 AN: 823319

Other (OTH) AF: 0.0000912 AC: 4 AN: 43864

GnomAD4 genome AF: 0.000239 AC: 27 AN: 112784 Hom.: 0 Cov.: 24 AF XY: 0.000200 AC XY: 7 AN XY: 34934

African (AFR) AF: 0.0000322 AC: 1 AN: 31056

American (AMR) AF: 0.00 AC: 0 AN: 10739

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3584

South Asian (SAS) AF: 0.00 AC: 0 AN: 2772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6223

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.000488 AC: 26 AN: 53313

Other (OTH) AF: 0.00 AC: 0 AN: 1524

Alfa AF: 0.00130 Hom.: 7

Bravo AF: 0.000110

ExAC AF: 0.0000577 AC: 7

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.794C>T (p.P265L) alteration is located in exon 12 (coding exon 12) of the CD99L2 gene. This alteration results from a C to T substitution at nucleotide position 794, causing the proline (P) at amino acid position 265 to be replaced by a leucine (L). 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	0.092
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T;.;.;.;.
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.58	T;T;T;T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.092	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.3	L;.;.;.;.
PhyloP100		0.44
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.26	N;.;N;N;N
REVEL	Benign	0.056
Sift	Uncertain	0.0080	D;.;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D;D
Polyphen		0.98	D;.;.;D;D
Vest4		0.31
MVP		0.14
MPC		0.095
ClinPred		0.054	T
GERP RS		0.63
Varity_R		0.091
gMVP		0.32
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

dbSNP: rs782752007; hg19: chrX-149937532;