chrX-150776287-A-G

Variant names:

• chrX-150776287-A-G
• rs781875770
• NM_031462.4:c.542T>C

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.542T>C​(p.Val181Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000183 in 1,204,215 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., 5 hem., cov: 23)
  • Exomes 𝑓: 0.0000092 (0 hom. 3 hem.)
• Consequence: CD99L2 NM_031462.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.970
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07212618).
• BS2: High Hemizygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD99L2	NM_031462.4	c.542T>C	p.Val181Ala	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.542T>C	p.Val181Ala	missense_variant	Exon 9 of 11	1	NM_031462.4	ENSP00000359403.3

Frequencies

GnomAD3 genomes AF: 0.000107 AC: 12 AN: 112223 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000357

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000933

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: 0.0000179 AC: 3 AN: 167373 AF XY: 0.0000369

Gnomad AFR exome AF: 0.0000808

Gnomad AMR exome AF: 0.0000393

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000136

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000916 AC: 10 AN: 1091992 Hom.: 0 Cov.: 30 AF XY: 0.00000838 AC XY: 3 AN XY: 357942

African (AFR) AF: 0.000305 AC: 8 AN: 26229

American (AMR) AF: 0.0000292 AC: 1 AN: 34258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19186

East Asian (EAS) AF: 0.00 AC: 0 AN: 29936

South Asian (SAS) AF: 0.00 AC: 0 AN: 53191

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40127

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4064

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 839174

Other (OTH) AF: 0.00 AC: 0 AN: 45827

GnomAD4 genome AF: 0.000107 AC: 12 AN: 112223 Hom.: 0 Cov.: 23 AF XY: 0.000145 AC XY: 5 AN XY: 34395

African (AFR) AF: 0.000357 AC: 11 AN: 30844

American (AMR) AF: 0.0000933 AC: 1 AN: 10716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3531

South Asian (SAS) AF: 0.00 AC: 0 AN: 2718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6165

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53167

Other (OTH) AF: 0.00 AC: 0 AN: 1508

Alfa AF: 0.000137 Hom.: 1

Bravo AF: 0.000117

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

Nov 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.554T>C (p.V185A) alteration is located in exon 9 (coding exon 9) of the CD99L2 gene. This alteration results from a T to C substitution at nucleotide position 554, causing the valine (V) at amino acid position 185 to be replaced by an alanine (A). 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	0.088
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	14
DANN	Benign	0.38
DEOGEN2	Benign	0.016	T;.;.;.;.
FATHMM_MKL	Benign	0.0022	N
LIST_S2	Benign	0.62	T;T;T;T;T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.072	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.75	N;.;.;.;.
PhyloP100		0.97
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.14	N;.;N;N;N
REVEL	Benign	0.011
Sift	Benign	0.48	T;.;T;T;T
Sift4G	Benign	0.20	T;T;T;T;T
Polyphen		0.27	B;.;.;B;B
Vest4		0.21
MutPred		0.21		Loss of sheet (P = 0.0084);.;.;.;.;
MVP		0.31
MPC		0.11
ClinPred		0.67	D
GERP RS		0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.035
gMVP		0.093
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: rs781875770; hg19: chrX-149944760; COSMIC: COSV60936124; COSMIC: COSV60936124;