rs548525038

Variant names:

• chr6-149942131-C-T
• rs548525038
• NM_025217.4:c.59C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_025217.4(ULBP2):​c.59C>T​(p.Ser20Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 1,611,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: ULBP2 NM_025217.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.849
• Publications: 1 publications found

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

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=0.041801155).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025217.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULBP2	NM_025217.4	MANE Select	c.59C>T	p.Ser20Phe	missense	Exon 1 of 5	NP_079493.1	Q9BZM5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULBP2	ENST00000367351.4	TSL:1 MANE Select	c.59C>T	p.Ser20Phe	missense	Exon 1 of 5	ENSP00000356320.3	Q9BZM5
	ULBP2	ENST00000948867.1		c.59C>T	p.Ser20Phe	missense	Exon 1 of 4	ENSP00000618926.1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000206 AC: 5 AN: 243012 AF XY: 0.00000757

Gnomad AFR exome AF: 0.0000656

Gnomad AMR exome AF: 0.0000588

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000504

Gnomad NFE exome AF: 0.00000909

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000356 AC: 52 AN: 1458706 Hom.: 0 Cov.: 33 AF XY: 0.0000372 AC XY: 27 AN XY: 725578

African (AFR) AF: 0.000150 AC: 5 AN: 33430

American (AMR) AF: 0.0000450 AC: 2 AN: 44430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39564

South Asian (SAS) AF: 0.00 AC: 0 AN: 85880

European-Finnish (FIN) AF: 0.0000191 AC: 1 AN: 52232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000360 AC: 40 AN: 1111076

Other (OTH) AF: 0.0000664 AC: 4 AN: 60250

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152336 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74494

African (AFR) AF: 0.0000962 AC: 4 AN: 41582

American (AMR) AF: 0.000196 AC: 3 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.9
DANN	Benign	0.69
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0099	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.00088	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.93	T
PhyloP100		-0.85
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.050
Sift	Benign	0.13	T
Sift4G	Benign	0.74	T
Polyphen		0.034	B
Vest4		0.14
MutPred		0.41		Loss of disorder (P = 0.025)
MVP		0.18
MPC		0.0044
ClinPred		0.053	T
GERP RS		1.1
PromoterAI		0.11	Neutral
Varity_R		0.055
gMVP		0.13
Mutation Taster		=98/2	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: rs548525038; hg19: chr6-150263267;