5-170252487-C-T

Position:

chr5-170252487-C-T

Variant summary

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

The NM_005565.5(LCP2):c.1270G>A(p.Val424Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000636 in 1,572,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

LCP2
NM_005565.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.16

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 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=0.22302696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCP2	NM_005565.5 link	c.1270G>A	p.Val424Ile	missense_variant	19/21	ENST00000046794.10	NP_005556.1	Q13094
LCP2	XM_047417171.1 link	c.1039G>A	p.Val347Ile	missense_variant	17/19		XP_047273127.1
C5orf58	NR_131091.3 link	n.1041C>T		non_coding_transcript_exon_variant	4/4
C5orf58	NR_131092.3 link	n.957C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LCP2	ENST00000046794.10 link	c.1270G>A	p.Val424Ile	missense_variant	19/21	1	NM_005565.5	ENSP00000046794.5	Q13094
C5orf58	ENST00000524171.5 link	c.*832C>T		3_prime_UTR_variant	4/4	1		ENSP00000490552.1	A0A1B0GVU6
LCP2	ENST00000521416.5 link	c.655G>A	p.Val219Ile	missense_variant	11/13	2		ENSP00000428871.1	E7ESF6

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000870

AC:

AN:

229834

Hom.:

AF XY:

0.0000161

AC XY:

AN XY:

124088

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000357

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000974

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000634

AC:

AN:

1420520

Hom.:

Cov.:

AF XY:

0.00000707

AC XY:

AN XY:

707442

show subpopulations

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:

0.0000240

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000649

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Jul 27, 2024

The c.1270G>A (p.V424I) alteration is located in exon 19 (coding exon 19) of the LCP2 gene. This alteration results from a G to A substitution at nucleotide position 1270, causing the valine (V) at amino acid position 424 to be replaced by an isoleucine (I). 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

0.072

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.52

D;T;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Uncertain

-0.12

MutationAssessor

Benign

1.3

L;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.20

N;.;N

REVEL

Benign

0.23

Sift

Benign

0.070

T;.;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.016

B;.;B

Vest4

0.18

MutPred

0.49

Loss of phosphorylation at Y426 (P = 0.1728);Loss of phosphorylation at Y426 (P = 0.1728);.;

MVP

0.64

MPC

0.16

ClinPred

0.28

GERP RS

3.2

Varity_R

0.024

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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