9-5557672-T-C

Variant names:

• chr9-5557672-T-C
• rs7854303
• NM_025239.4:c.686T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025239.4(PDCD1LG2):​c.686T>C​(p.Phe229Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,613,858 control chromosomes in the GnomAD database, including 805,838 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 1.0 (75927 hom., cov: 32)
  • Exomes 𝑓: 1.0 (729911 hom.)
• Consequence: PDCD1LG2 NM_025239.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.676

Genes affected

PDCD1LG2 (HGNC:18731): (programmed cell death 1 ligand 2) Involved in negative regulation of activated T cell proliferation; negative regulation of interferon-gamma production; and negative regulation of interleukin-10 production. Predicted to be located in plasma membrane. Predicted to be active in external side of plasma membrane. Biomarker of pulmonary tuberculosis. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286162 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.293073E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD1LG2	NM_025239.4	c.686T>C	p.Phe229Ser	missense_variant	Exon 5 of 7	ENST00000397747.5	NP_079515.2
PDCD1LG2	XM_005251600.4	c.686T>C	p.Phe229Ser	missense_variant	Exon 5 of 7		XP_005251657.1
LOC124902114	XR_007061406.1	n.162-33043A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD1LG2	ENST00000397747.5	c.686T>C	p.Phe229Ser	missense_variant	Exon 5 of 7	1	NM_025239.4	ENSP00000380855.3
ENSG00000286162	ENST00000661858.1	n.183-33043A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.998 AC: 151981 AN: 152230 Hom.: 75867 Cov.: 32

Gnomad AFR AF: 0.997

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.996

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.996

GnomAD3 exomes AF: 0.999 AC: 251059 AN: 251294 Hom.: 125413 AF XY: 0.999 AC XY: 135685 AN XY: 135808

Gnomad AFR exome AF: 0.997

Gnomad AMR exome AF: 0.997

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.998

GnomAD4 exome AF: 0.999 AC: 1460664 AN: 1461510 Hom.: 729911 Cov.: 53 AF XY: 0.999 AC XY: 726657 AN XY: 727088

Gnomad4 AFR exome AF: 0.996

Gnomad4 AMR exome AF: 0.997

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.998

GnomAD4 genome AF: 0.998 AC: 152100 AN: 152348 Hom.: 75927 Cov.: 32 AF XY: 0.998 AC XY: 74373 AN XY: 74498

Gnomad4 AFR AF: 0.997

Gnomad4 AMR AF: 0.996

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.996

Alfa AF: 0.915 Hom.: 34999

Bravo AF: 0.998

TwinsUK AF: 1.00 AC: 3707

ALSPAC AF: 1.00 AC: 3853

ESP6500AA AF: 0.998 AC: 4396

ESP6500EA AF: 0.999 AC: 8594

ExAC AF: 0.999 AC: 121310

Asia WGS AF: 1.00 AC: 3478 AN: 3478

EpiCase AF: 0.999

EpiControl AF: 0.999

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.0
DANN	Benign	0.17
DEOGEN2	Benign	0.048	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00063	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	8.3e-7	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.29	T
PROVEAN	Benign	2.0	N
REVEL	Benign	0.029
Sift	Benign	0.55	T
Sift4G	Benign	0.82	T
Polyphen		0.0	B
Vest4		0.029
MPC		0.043
ClinPred		0.0019	T
GERP RS		0.72
Varity_R		0.045
gMVP		0.28

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

LitVar

Other links and lift over

dbSNP: rs7854303; hg19: chr9-5557672;