1-116764502-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001767.5(CD2):c.632A>C(p.Tyr211Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,794 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CD2 NM_001767.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.118

Genes affected

CD2 (HGNC:1639): (CD2 molecule) The protein encoded by this gene is a surface antigen found on all peripheral blood T-cells. The encoded protein interacts with LFA3 (CD58) on antigen presenting cells to optimize immune recognition. A locus control region (LCR) has been found in the 3' flanking sequence of this gene. [provided by RefSeq, Jun 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD2	NM_001767.5	c.632A>C	p.Tyr211Ser	missense_variant	4/5	ENST00000369478.4
CD2	NM_001328609.2	c.710A>C	p.Tyr237Ser	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD2	ENST00000369478.4	c.632A>C	p.Tyr211Ser	missense_variant	4/5	1	NM_001767.5	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461794 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727198

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

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

Jun 30, 2023

The c.632A>C (p.Y211S) alteration is located in exon 4 (coding exon 4) of the CD2 gene. This alteration results from a A to C substitution at nucleotide position 632, causing the tyrosine (Y) at amino acid position 211 to be replaced by a serine (S). 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	-0.013	T
BayesDel_noAF	Benign	-0.26
Cadd	Benign	17
Dann	Benign	0.95
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Benign	0.29
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.45
MutPred		0.45		Loss of stability (P = 0.0201);
MVP		0.86
MPC		0.12
ClinPred		0.98	D
GERP RS		-1.3
Varity_R		0.35
gMVP		0.63

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-117307124;