Variant 5-170253135-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005565.5(LCP2):c.1229C>G(p.Ser410Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0162 in 1,609,648 control chromosomes in the GnomAD database, including 263 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.012 ( 18 hom., cov: 33)

Exomes 𝑓: 0.017 ( 245 hom. )

Consequence

LCP2
NM_005565.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.04

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:

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=0.0049465597).

BP6

Variant 5-170253135-G-C is Benign according to our data. Variant chr5-170253135-G-C is described in ClinVar as [Benign]. Clinvar id is 2656067.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0117 (1775/152284) while in subpopulation NFE AF= 0.0176 (1200/68022). AF 95% confidence interval is 0.0168. There are 18 homozygotes in gnomad4. There are 806 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP2	NM_005565.5 link	c.1229C>G	p.Ser410Cys	missense_variant	Exon 18 of 21	ENST00000046794.10	NP_005556.1	Q13094
LCP2	XM_047417171.1 link	c.998C>G	p.Ser333Cys	missense_variant	Exon 16 of 19		XP_047273127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCP2	ENST00000046794.10 link	c.1229C>G	p.Ser410Cys	missense_variant	Exon 18 of 21	1	NM_005565.5	ENSP00000046794.5		Q13094
LCP2	ENST00000521416.5 link	c.614C>G	p.Ser205Cys	missense_variant	Exon 10 of 13	2		ENSP00000428871.1		E7ESF6

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1775

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00285

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00913

Gnomad FIN

AF:

0.0149

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0176

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0122

AC:

2980

AN:

244384

Hom.:

AF XY:

0.0122

AC XY:

1619

AN XY:

132346

show subpopulations

Gnomad AFR exome

AF:

0.00362

Gnomad AMR exome

AF:

0.00796

Gnomad ASJ exome

AF:

0.0142

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00930

Gnomad FIN exome

AF:

0.0129

Gnomad NFE exome

AF:

0.0171

Gnomad OTH exome

AF:

0.0127

GnomAD4 exome

AF:

0.0167

AC:

24363

AN:

1457364

Hom.:

245

Cov.:

AF XY:

0.0165

AC XY:

11936

AN XY:

724726

show subpopulations

Gnomad4 AFR exome

AF:

0.00278

Gnomad4 AMR exome

AF:

0.00930

Gnomad4 ASJ exome

AF:

0.0143

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00916

Gnomad4 FIN exome

AF:

0.0136

Gnomad4 NFE exome

AF:

0.0189

Gnomad4 OTH exome

AF:

0.0154

GnomAD4 genome

AF:

0.0117

AC:

1775

AN:

152284

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

806

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00284

Gnomad4 AMR

AF:

0.0122

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00914

Gnomad4 FIN

AF:

0.0149

Gnomad4 NFE

AF:

0.0176

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0161

Hom.:

Bravo

AF:

0.0112

TwinsUK

AF:

0.0216

AC:

ALSPAC

AF:

0.0202

AC:

ESP6500AA

AF:

0.00385

AC:

ESP6500EA

AF:

0.0201

AC:

164

ExAC

AF:

0.0118

AC:

1422

Asia WGS

AF:

0.00260

AC:

AN:

3478

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

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

LCP2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.64

D;T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.58

T;T;T

MetaRNN

Benign

0.0049

T;T;T

MetaSVM

Uncertain

-0.10

MutationAssessor

Uncertain

2.0

M;.;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.0

N;.;N

REVEL

Benign

0.19

Sift

Uncertain

0.010

D;.;D

Sift4G

Benign

0.069

T;D;D

Polyphen

1.0

D;.;D

Vest4

0.16

MPC

0.38

ClinPred

0.014

GERP RS

3.5

Varity_R

0.049

gMVP

0.45

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