Variant chr6-149947338-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_025217.4(ULBP2):c.650C>T(p.Ser217Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,542,870 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 78 hom., cov: 28)

Exomes 𝑓: 0.0017 ( 66 hom. )

Consequence

ULBP2
NM_025217.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.572

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028360784).

BP6

Variant 6-149947338-C-T is Benign according to our data. Variant chr6-149947338-C-T is described in ClinVar as [Benign]. Clinvar id is 776171.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ULBP2	NM_025217.4 linkuse as main transcript	c.650C>T	p.Ser217Leu	missense_variant	4/5	ENST00000367351.4
ULBP2	XM_047419377.1 linkuse as main transcript	c.650C>T	p.Ser217Leu	missense_variant	4/4
ULBP2	XM_017011321.2 linkuse as main transcript	c.631+685C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ULBP2	ENST00000367351.4 linkuse as main transcript	c.650C>T	p.Ser217Leu	missense_variant	4/5	1	NM_025217.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0162

AC:

2420

AN:

149232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0580

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00540

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000435

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.00980

GnomAD3 exomes

AF:

0.00425

AC:

538

AN:

126584

Hom.:

AF XY:

0.00338

AC XY:

216

AN XY:

63906

show subpopulations

Gnomad AFR exome

AF:

0.0561

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000700

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000615

Gnomad OTH exome

AF:

0.00169

GnomAD4 exome

AF:

0.00165

AC:

2303

AN:

1393526

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

974

AN XY:

688904

show subpopulations

Gnomad4 AFR exome

AF:

0.0609

Gnomad4 AMR exome

AF:

0.00285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000507

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000271

Gnomad4 OTH exome

AF:

0.00356

GnomAD4 genome

AF:

0.0163

AC:

2429

AN:

149344

Hom.:

Cov.:

AF XY:

0.0157

AC XY:

1145

AN XY:

72828

show subpopulations

Gnomad4 AFR

AF:

0.0580

Gnomad4 AMR

AF:

0.00539

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000652

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000133

Gnomad4 OTH

AF:

0.00971

Alfa

AF:

0.00549

Hom.:

Bravo

AF:

0.0184

ESP6500AA

AF:

0.00940

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00264

AC:

301

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.019

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0028

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.7

REVEL

Benign

0.016

Sift

Benign

0.19

Sift4G

Benign

0.11

Polyphen

0.0090

Vest4

0.080

MVP

0.14

MPC

0.033

ClinPred

0.0026

GERP RS

1.4

Varity_R

0.032

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over