Variant chr5-170253130-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005565.5(LCP2):c.1234G>A(p.Ala412Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000033 in 1,456,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

LCP2
NM_005565.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053593487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCP2	NM_005565.5 linkuse as main transcript	c.1234G>A	p.Ala412Thr	missense_variant	18/21	ENST00000046794.10	NP_005556.1
LCP2	XM_047417171.1 linkuse as main transcript	c.1003G>A	p.Ala335Thr	missense_variant	16/19		XP_047273127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCP2	ENST00000046794.10 linkuse as main transcript	c.1234G>A	p.Ala412Thr	missense_variant	18/21	1	NM_005565.5	ENSP00000046794	P1
LCP2	ENST00000521416.5 linkuse as main transcript	c.619G>A	p.Ala207Thr	missense_variant	10/13	2		ENSP00000428871

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000206

AC:

AN:

243164

Hom.:

AF XY:

0.0000304

AC XY:

AN XY:

131738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000565

Gnomad SAS exome

AF:

0.0000339

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000330

AC:

AN:

1456344

Hom.:

Cov.:

AF XY:

0.0000345

AC XY:

AN XY:

724158

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000587

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000298

Gnomad4 OTH exome

AF:

0.0000665

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.1234G>A (p.A412T) alteration is located in exon 18 (coding exon 18) of the LCP2 gene. This alteration results from a G to A substitution at nucleotide position 1234, causing the alanine (A) at amino acid position 412 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.37

T;T;T

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.054

T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

0.0

N;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.46

N;.;N

REVEL

Benign

0.064

Sift

Benign

0.26

T;.;T

Sift4G

Benign

0.66

T;T;T

Polyphen

0.0010

B;.;B

Vest4

0.084

MutPred

0.24

Gain of phosphorylation at A412 (P = 0.0117);Gain of phosphorylation at A412 (P = 0.0117);.;

MVP

0.42

MPC

0.17

ClinPred

0.026

GERP RS

3.0

Varity_R

0.026

gMVP

0.37

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