X-150770325-C-T

Position:

• chrX-150770325-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_031462.4(CD99L2):​c.700G>A​(p.Val234Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000246 in 1,097,935 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.000025 (0 hom. 11 hem.)
• Consequence: CD99L2 NM_031462.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.42

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD99L2	NM_031462.4	c.700G>A	p.Val234Met	missense_variant	10/11	ENST00000370377.8	NP_113650.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD99L2	ENST00000370377.8	c.700G>A	p.Val234Met	missense_variant	10/11	1	NM_031462.4	ENSP00000359403.3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.00000545 AC: 1 AN: 183341 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 67783

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000246 AC: 27 AN: 1097935 Hom.: 0 Cov.: 29 AF XY: 0.0000303 AC XY: 11 AN XY: 363293

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: 0.0000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000297

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2022

The c.730G>A (p.V244M) alteration is located in exon 11 (coding exon 11) of the CD99L2 gene. This alteration results from a G to A substitution at nucleotide position 730, causing the valine (V) at amino acid position 244 to be replaced by a methionine (M). 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	0.29
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.;.;.;.
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D;D;D;D;D
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.62	D;D;D;D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.1	M;.;.;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.7	N;.;N;N;N
REVEL	Benign	0.29
Sift	Uncertain	0.0020	D;.;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D;D
Polyphen		1.0	D;.;.;D;D
Vest4		0.66
MutPred		0.30		Gain of disorder (P = 0.1358);.;.;.;.;
MVP		0.44
MPC		0.43
ClinPred		0.90	D
GERP RS		4.2
Varity_R		0.30
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.40		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.40		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1557418987; hg19: chrX-149938798; COSMIC: COSV60935281;