Genetic Variant NM_025217.4:c.152C>A (chr6-149945375-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025217.4(ULBP2):c.152C>A(p.Ala51Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,526 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. 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. A51V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ULBP2
NM_025217.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.40

Publications

0 publications found

Variant links:

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]

ULBP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.048503816).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULBP2	NM_025217.4 link	c.152C>A	p.Ala51Glu	missense_variant	Exon 2 of 5	ENST00000367351.4	NP_079493.1	Q9BZM5
ULBP2	XM_047419377.1 link	c.152C>A	p.Ala51Glu	missense_variant	Exon 2 of 4		XP_047275333.1
ULBP2	XM_017011321.2 link	c.152C>A	p.Ala51Glu	missense_variant	Exon 2 of 4		XP_016866810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULBP2	ENST00000367351.4 link	c.152C>A	p.Ala51Glu	missense_variant	Exon 2 of 5	1	NM_025217.4	ENSP00000356320.3		Q9BZM5

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151892

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250592

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000625

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460634

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726670

show subpopulations

African (AFR)

AF:

0.0000897

AC:

AN:

33436

American (AMR)

AF:

0.0000224

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4934

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111834

Other (OTH)

AF:

0.00

AC:

AN:

60268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151892

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41264

American (AMR)

AF:

0.0000656

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.0060

(source)

DANN

Benign

0.21

DEOGEN2

Benign

0.0023

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00060

LIST_S2

Benign

0.67

M_CAP

Benign

0.0013

MetaRNN

Benign

0.049

MetaSVM

Benign

-0.90

PhyloP100

-1.4

PrimateAI

Benign

0.23

PROVEAN

Benign

2.7

REVEL

Benign

0.025

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.013

Vest4

0.075

MutPred

0.65

Gain of sheet (P = 0.1451);

MVP

0.076

MPC

1.4

ClinPred

0.021

GERP RS

-4.2

Varity_R

0.060

gMVP

0.24

Mutation Taster

=100/0

polymorphism

(source)

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

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NM_025217.4:c.152C>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over