Variant 5-170248735-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000046794.10(LCP2):c.1564T>C(p.Tyr522His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00328 in 1,610,636 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 13 hom. )

Consequence

LCP2
ENST00000046794.10 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.08

Variant links:

Genes affected

LCP2 (HGNC:6529): (lymphocyte cytosolic protein 2) This gene encodes an adapter protein that acts as a substrate of the T cell antigen receptor (TCR)-activated protein tyrosine kinase pathway. The encoded protein associates with growth factor receptor bound protein 2, and is thought to play a role TCR-mediated intracellular signal transduction. A similar protein in mouse plays a role in normal T-cell development and activation. Mice lacking this gene show subcutaneous and intraperitoneal fetal hemorrhaging, dysfunctional platelets and impaired viability. [provided by RefSeq, Nov 2016]

LCP2 links:

C5orf58 (HGNC:37272): (chromosome 5 open reading frame 58)

C5orf58 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005723983).

BP6

Variant 5-170248735-A-G is Benign according to our data. Variant chr5-170248735-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2656066.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LCP2	NM_005565.5 linkuse as main transcript	c.1564T>C	p.Tyr522His	missense_variant	21/21	ENST00000046794.10	NP_005556.1
LCP2	XM_047417171.1 linkuse as main transcript	c.1333T>C	p.Tyr445His	missense_variant	19/19		XP_047273127.1
C5orf58	NR_131091.3 linkuse as main transcript	n.202-2913A>G		intron_variant, non_coding_transcript_variant
C5orf58	NR_131092.3 linkuse as main transcript	n.118-2913A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCP2	ENST00000046794.10 linkuse as main transcript	c.1564T>C	p.Tyr522His	missense_variant	21/21	1	NM_005565.5	ENSP00000046794	P1

Frequencies

GnomAD3 genomes

AF:

0.00264

AC:

402

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00349

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00440

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00268

AC:

658

AN:

245588

Hom.:

AF XY:

0.00269

AC XY:

358

AN XY:

133284

show subpopulations

Gnomad AFR exome

AF:

0.000521

Gnomad AMR exome

AF:

0.000479

Gnomad ASJ exome

AF:

0.00282

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00101

Gnomad FIN exome

AF:

0.00363

Gnomad NFE exome

AF:

0.00426

Gnomad OTH exome

AF:

0.00352

GnomAD4 exome

AF:

0.00334

AC:

4877

AN:

1458358

Hom.:

Cov.:

AF XY:

0.00332

AC XY:

2410

AN XY:

725412

show subpopulations

Gnomad4 AFR exome

AF:

0.000813

Gnomad4 AMR exome

AF:

0.000525

Gnomad4 ASJ exome

AF:

0.00254

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000773

Gnomad4 FIN exome

AF:

0.00306

Gnomad4 NFE exome

AF:

0.00393

Gnomad4 OTH exome

AF:

0.00256

GnomAD4 genome

AF:

0.00265

AC:

403

AN:

152278

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

186

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00349

Gnomad4 NFE

AF:

0.00440

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00365

Hom.:

Bravo

AF:

0.00239

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000253

AC:

ESP6500EA

AF:

0.00507

AC:

ExAC

AF:

0.00299

AC:

361

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00349

EpiControl

AF:

0.00416

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

LCP2: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;T;T

Eigen

Benign

-0.079

Eigen_PC

Benign

0.044

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.0076

MetaRNN

Benign

0.0057

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.90

N;.;.

MutationTaster

Benign

0.56

N;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.92

N;.;N

REVEL

Benign

0.11

Sift

Benign

0.26

T;.;T

Sift4G

Benign

0.18

T;T;T

Polyphen

0.90

P;.;P

Vest4

0.22

MVP

0.47

MPC

0.69

ClinPred

0.023

GERP RS

3.1

Varity_R

0.031

gMVP

0.33

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

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