rs2228315

Variant names:

• chr12-108624122-C-A
• rs2228315
• NM_003006.4:c.186G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-108624122-C-A
• chr12-108624122-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003006.4(SELPLG):​c.186G>T​(p.Met62Ile) 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 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SELPLG NM_003006.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.977
• Publications: 0 publications found

Genes affected

SELPLG (HGNC:10722): (selectin P ligand) This gene encodes a glycoprotein that functions as a high affinity counter-receptor for the cell adhesion molecules P-, E- and L- selectin expressed on myeloid cells and stimulated T lymphocytes. As such, this protein plays a critical role in leukocyte trafficking during inflammation by tethering of leukocytes to activated platelets or endothelia expressing selectins. This protein requires two post-translational modifications, tyrosine sulfation and the addition of the sialyl Lewis x tetrasaccharide (sLex) to its O-linked glycans, for its high-affinity binding activity. Aberrant expression of this gene and polymorphisms in this gene are associated with defects in the innate and adaptive immune response. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.020554006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELPLG	NM_003006.4	c.186G>T	p.Met62Ile	missense_variant	Exon 2 of 2	ENST00000550948.2	NP_002997.2
SELPLG	NM_001206609.2	c.234G>T	p.Met78Ile	missense_variant	Exon 2 of 2		NP_001193538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELPLG	ENST00000550948.2	c.186G>T	p.Met62Ile	missense_variant	Exon 2 of 2	1	NM_003006.4	ENSP00000447752.1
SELPLG	ENST00000228463.7	c.234G>T	p.Met78Ile	missense_variant	Exon 2 of 2	2		ENSP00000228463.6
SELPLG	ENST00000388962.4	c.186G>T	p.Met62Ile	missense_variant	Exon 1 of 2	5		ENSP00000373614.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461880 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.050
DANN	Benign	0.54
DEOGEN2	Benign	0.034	T;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.26	T;T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.021	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.58	N;.;.
PhyloP100		-0.98
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.070	N;N;N
REVEL	Benign	0.0060
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.78	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.015
MutPred		0.32		Gain of catalytic residue at P59 (P = 2e-04);Gain of catalytic residue at P59 (P = 2e-04);.;
MVP		0.12
MPC		0.12
ClinPred		0.027	T
GERP RS		-1.8
PromoterAI		-0.024	Neutral
Varity_R		0.020
gMVP		0.091
Mutation Taster		=100/0	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: rs2228315; hg19: chr12-109017898;