chr3-108355258-G-T

Variant names:

• chr3-108355258-G-T
• rs201761554
• NM_001282556.2:c.562G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001282556.2(HHLA2):​c.562G>T​(p.Gly188Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. G188R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HHLA2 NM_001282556.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• Publications: 1 publications found

Genes affected

HHLA2 (HGNC:4905): (HHLA2 member of B7 family) This gene encodes a protein ligand found on the surface of monocytes. The encoded protein is thought to regulate cell-mediated immunity by binding to a receptor on T lymphocytes and inhibiting the proliferation of these cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17265683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HHLA2	NM_001282556.2	c.562G>T	p.Gly188Trp	missense_variant	Exon 5 of 10	ENST00000467761.6	NP_001269485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HHLA2	ENST00000467761.6	c.562G>T	p.Gly188Trp	missense_variant	Exon 5 of 10	5	NM_001282556.2	ENSP00000419207.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0044	T;T;.;T;T;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.70	T;T;T;.;.;.
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.17	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;.;.;M;M;M
PhyloP100		0.11
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	.;N;N;N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.0050	.;D;D;D;D;D
Sift4G	Uncertain	0.014	D;D;D;D;D;D
Polyphen		1.0	D;D;.;D;D;D
Vest4		0.22
MutPred		0.56		Loss of disorder (P = 0.0244);Loss of disorder (P = 0.0244);.;Loss of disorder (P = 0.0244);Loss of disorder (P = 0.0244);Loss of disorder (P = 0.0244);
MVP		0.31
MPC		0.37
ClinPred		0.22	T
GERP RS		0.23
Varity_R		0.077
gMVP		0.31
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs201761554; hg19: chr3-108074105;