X-150770349-C-T

Variant names:

• chrX-150770349-C-T
• rs782177062
• NM_031462.4:c.676G>A

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.676G>A​(p.Val226Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,210,269 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 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 0.000053 (0 hom., 1 hem., cov: 25)
  • 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: 2.84
• 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=0.123751014).
• BS2: High Hemizygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD99L2	NM_031462.4	c.676G>A	p.Val226Met	missense_variant	Exon 10 of 11	ENST00000370377.8	NP_113650.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD99L2	ENST00000370377.8	c.676G>A	p.Val226Met	missense_variant	Exon 10 of 11	1	NM_031462.4	ENSP00000359403.3

Frequencies

GnomAD3 genomes AF: 0.0000534 AC: 6 AN: 112355 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000647

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000279

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00133

GnomAD2 exomes AF: 0.0000436 AC: 8 AN: 183316 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000611

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.0000246 AC: 27 AN: 1097862 Hom.: 0 Cov.: 29 AF XY: 0.0000303 AC XY: 11 AN XY: 363228

African (AFR) AF: 0.00 AC: 0 AN: 26397

American (AMR) AF: 0.0000284 AC: 1 AN: 35202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.0000662 AC: 2 AN: 30203

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54127

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40505

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4131

European-Non Finnish (NFE) AF: 0.0000178 AC: 15 AN: 841831

Other (OTH) AF: 0.000152 AC: 7 AN: 46083

GnomAD4 genome AF: 0.0000534 AC: 6 AN: 112407 Hom.: 0 Cov.: 25 AF XY: 0.0000289 AC XY: 1 AN XY: 34583

African (AFR) AF: 0.0000646 AC: 2 AN: 30967

American (AMR) AF: 0.00 AC: 0 AN: 10694

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

East Asian (EAS) AF: 0.000280 AC: 1 AN: 3574

South Asian (SAS) AF: 0.00 AC: 0 AN: 2679

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6155

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 215

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53258

Other (OTH) AF: 0.00131 AC: 2 AN: 1523

Alfa AF: 0.000130 Hom.: 1

Bravo AF: 0.0000604

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.706G>A (p.V236M) 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 706, causing the valine (V) at amino acid position 236 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	0.19
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	T;.;.;.;.
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	D;T;D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;.;.;.;.
PhyloP100		2.8
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.4	N;.;N;N;N
REVEL	Benign	0.069
Sift	Uncertain	0.028	D;.;T;T;T
Sift4G	Benign	0.097	T;T;T;T;T
Polyphen		0.93	P;.;.;D;D
Vest4		0.51
MVP		0.71
MPC		0.42
ClinPred		0.17	T
GERP RS		5.1
Varity_R		0.11
gMVP		0.55
Mutation Taster		=97/3	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: rs782177062; hg19: chrX-149938822;