chrX-150769049-T-G

Variant names:

• chrX-150769049-T-G
• rs782154388
• NM_031462.4:c.774A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031462.4(CD99L2):​c.774A>C​(p.Glu258Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,155,186 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.0000019 (0 hom. 0 hem.)
• Consequence: CD99L2 NM_031462.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.780
• Publications: 1 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.067359984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD99L2	NM_031462.4	c.774A>C	p.Glu258Asp	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.774A>C	p.Glu258Asp	missense_variant	Exon 11 of 11	1	NM_031462.4	ENSP00000359403.3

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112635 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000645

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000156 AC: 2 AN: 128528 AF XY: 0.00

Gnomad AFR exome AF: 0.000203

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000192 AC: 2 AN: 1042551 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 340003

African (AFR) AF: 0.0000898 AC: 2 AN: 22284

American (AMR) AF: 0.00 AC: 0 AN: 21120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17446

East Asian (EAS) AF: 0.00 AC: 0 AN: 26537

South Asian (SAS) AF: 0.00 AC: 0 AN: 46111

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3902

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 822875

Other (OTH) AF: 0.00 AC: 0 AN: 43804

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112635 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34793

African (AFR) AF: 0.0000645 AC: 2 AN: 30998

American (AMR) AF: 0.00 AC: 0 AN: 10718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2656

East Asian (EAS) AF: 0.00 AC: 0 AN: 3575

South Asian (SAS) AF: 0.00 AC: 0 AN: 2767

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53287

Other (OTH) AF: 0.00 AC: 0 AN: 1519

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.804A>C (p.E268D) alteration is located in exon 12 (coding exon 12) of the CD99L2 gene. This alteration results from a A to C substitution at nucleotide position 804, causing the glutamic acid (E) at amino acid position 268 to be replaced by an aspartic acid (D). 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	-0.66	T
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.52
DANN	Benign	0.95
DEOGEN2	Benign	0.025	T;.;.;.;.
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.63	T;T;T;T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.067	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;.;.;.
PhyloP100		-0.78
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.95	N;.;N;N;N
REVEL	Benign	0.019
Sift	Benign	0.034	D;.;D;D;D
Sift4G	Benign	0.087	T;T;T;T;T
Polyphen		0.027	B;.;.;B;B
Vest4		0.049
MutPred		0.083		Gain of helix (P = 0.0854);.;.;.;.;
MVP		0.43
MPC		0.25
ClinPred		0.023	T
GERP RS		-1.8
Varity_R		0.094
gMVP		0.10
Mutation Taster		=95/5	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: rs782154388; hg19: chrX-149937522;