rs782209079

Variant names:

• chrX-150793736-C-G
• rs782209079
• NM_031462.4:c.451G>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.451G>C​(p.Glu151Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000925 in 1,081,289 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.0000092 (0 hom. 3 hem.)
  • Failed GnomAD Quality Control
• Consequence: CD99L2 NM_031462.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92
• 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=0.12859797).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD99L2	NM_031462.4	c.451G>C	p.Glu151Gln	missense_variant	Exon 7 of 11	ENST00000370377.8	NP_113650.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD99L2	ENST00000370377.8	c.451G>C	p.Glu151Gln	missense_variant	Exon 7 of 11	1	NM_031462.4	ENSP00000359403.3

Frequencies

GnomAD3 genomes AF: 0.00000894 AC: 1 AN: 111845 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000280

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: 0.0000481 AC: 8 AN: 166321 AF XY: 0.0000186

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000588

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000925 AC: 10 AN: 1081289 Hom.: 0 Cov.: 27 AF XY: 0.00000859 AC XY: 3 AN XY: 349363

African (AFR) AF: 0.00 AC: 0 AN: 25726

American (AMR) AF: 0.00 AC: 0 AN: 32780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18900

East Asian (EAS) AF: 0.000307 AC: 9 AN: 29344

South Asian (SAS) AF: 0.00 AC: 0 AN: 50754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4055

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 834275

Other (OTH) AF: 0.0000221 AC: 1 AN: 45315

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000894 AC: 1 AN: 111895 Hom.: 0 Cov.: 23 AF XY: 0.0000293 AC XY: 1 AN XY: 34091

African (AFR) AF: 0.00 AC: 0 AN: 30764

American (AMR) AF: 0.00 AC: 0 AN: 10557

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

East Asian (EAS) AF: 0.000281 AC: 1 AN: 3557

South Asian (SAS) AF: 0.00 AC: 0 AN: 2688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53158

Other (OTH) AF: 0.00 AC: 0 AN: 1511

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000412 AC: 5

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.463G>C (p.E155Q) alteration is located in exon 7 (coding exon 7) of the CD99L2 gene. This alteration results from a G to C substitution at nucleotide position 463, causing the glutamic acid (E) at amino acid position 155 to be replaced by a glutamine (Q). 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	0.19
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;.;.;.
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.8	M;.;.;.
PhyloP100		1.9
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.8	N;.;N;N
REVEL	Benign	0.085
Sift	Benign	0.20	T;.;T;T
Sift4G	Benign	0.088	T;T;T;T
Polyphen		1.0	D;.;D;P
Vest4		0.27
MutPred		0.17		Gain of methylation at K148 (P = 0.1134);.;.;.;
MVP		0.51
MPC		0.33
ClinPred		0.40	T
GERP RS		3.0
Varity_R		0.25
gMVP		0.11
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs782209079; hg19: chrX-149962209;