rs548525038

Variant names:

• chr6-149942131-C-A
• NM_025217.4:c.59C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-149942131-C-A
• chr6-149942131-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025217.4(ULBP2):​c.59C>A​(p.Ser20Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. S20F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ULBP2 NM_025217.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.849

Genes affected

ULBP2 (HGNC:14894): (UL16 binding protein 2) This gene encodes a major histocompatibility complex (MHC) class I-related molecule that binds to the NKG2D receptor on natural killer (NK) cells to trigger release of multiple cytokines and chemokines that in turn contribute to the recruitment and activation of NK cells. The encoded protein undergoes further processing to generate the mature protein that is either anchored to membrane via a glycosylphosphatidylinositol moiety, or secreted. Many malignant cells secrete the encoded protein to evade immunosurveillance by NK cells. This gene is located in a cluster of multiple MHC class I-related genes on chromosome 6. [provided by RefSeq, Jul 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12527773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULBP2	NM_025217.4	c.59C>A	p.Ser20Tyr	missense_variant	Exon 1 of 5	ENST00000367351.4	NP_079493.1
ULBP2	XM_047419377.1	c.59C>A	p.Ser20Tyr	missense_variant	Exon 1 of 4		XP_047275333.1
ULBP2	XM_017011321.2	c.59C>A	p.Ser20Tyr	missense_variant	Exon 1 of 4		XP_016866810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULBP2	ENST00000367351.4	c.59C>A	p.Ser20Tyr	missense_variant	Exon 1 of 5	1	NM_025217.4	ENSP00000356320.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458706 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 725578

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.5
DANN	Benign	0.48
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.00096	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.92	T
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.078
Sift	Benign	0.12	T
Sift4G	Benign	1.0	T
Polyphen		0.88	P
Vest4		0.18
MutPred		0.42		Loss of disorder (P = 0.0411);
MVP		0.25
MPC		0.0088
ClinPred		0.19	T
GERP RS		1.1
Varity_R		0.056
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr6-150263267;