Variant 5-170252478-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005565.5(LCP2):c.1279A>G(p.Ile427Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LCP2
NM_005565.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.15

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19229463).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LCP2	NM_005565.5 linkuse as main transcript	c.1279A>G	p.Ile427Val	missense_variant	19/21	ENST00000046794.10
LCP2	XM_047417171.1 linkuse as main transcript	c.1048A>G	p.Ile350Val	missense_variant	17/19
C5orf58	NR_131091.3 linkuse as main transcript	n.1032T>C		non_coding_transcript_exon_variant	4/4
C5orf58	NR_131092.3 linkuse as main transcript	n.948T>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LCP2	ENST00000046794.10 linkuse as main transcript	c.1279A>G	p.Ile427Val	missense_variant	19/21	1	NM_005565.5	P1
C5orf58	ENST00000524171.5 linkuse as main transcript	c.*823T>C		3_prime_UTR_variant	4/4	1
LCP2	ENST00000521416.5 linkuse as main transcript	c.664A>G	p.Ile222Val	missense_variant	11/13	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1432644

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713008

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Immunodeficiency 81

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Nov 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Uncertain

0.073

BayesDel_noAF

Benign

-0.13

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Uncertain

0.54

D;T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.62

T;T;T

M_CAP

Benign

0.053

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

0.97

L;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.12

N;.;N

REVEL

Uncertain

0.34

Sift

Benign

0.38

T;.;T

Sift4G

Benign

0.68

T;T;T

Polyphen

0.0050

B;.;B

Vest4

0.28

MutPred

0.71

Gain of phosphorylation at Y423 (P = 0.0936);Gain of phosphorylation at Y423 (P = 0.0936);.;

MVP

0.78

MPC

0.16

ClinPred

0.13

GERP RS

3.8

Varity_R

0.030

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over