Genetic Variant LCP2:p.Val424Leu (chr5-170252487-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_005565.5(LCP2):c.1270G>C(p.Val424Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,420,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V424I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

LCP2
NM_005565.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.16

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38385627).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005565.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LCP2	NM_005565.5	MANE Select	c.1270G>C	p.Val424Leu	missense	Exon 19 of 21	NP_005556.1	Q13094
C5orf58	NR_131091.3		n.1041C>G		non_coding_transcript_exon	Exon 4 of 4
C5orf58	NR_131092.3		n.957C>G		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LCP2	ENST00000046794.10	TSL:1 MANE Select	c.1270G>C	p.Val424Leu	missense	Exon 19 of 21	ENSP00000046794.5	Q13094
C5orf58	ENST00000524171.5	TSL:1	c.*832C>G		3_prime_UTR	Exon 4 of 4	ENSP00000490552.1	A0A1B0GVU6
LCP2	ENST00000968849.1		c.1279G>C	p.Val427Leu	missense	Exon 19 of 21	ENSP00000638908.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000435

AC:

AN:

229834

AF XY:

0.00000806

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000974

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.04e-7

AC:

AN:

1420520

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

707442

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32640

American (AMR)

AF:

0.00

AC:

AN:

43214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25672

East Asian (EAS)

AF:

0.00

AC:

AN:

39334

South Asian (SAS)

AF:

0.00

AC:

AN:

83378

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1079040

Other (OTH)

AF:

0.00

AC:

AN:

58898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.71

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.040

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.64

M_CAP

Benign

0.051

MetaRNN

Benign

0.38

MetaSVM

Uncertain

0.17

MutationAssessor

Benign

0.95

PhyloP100

2.2

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.7

REVEL

Uncertain

0.49

Sift

Benign

0.15

Sift4G

Benign

0.11

Polyphen

0.031

Vest4

0.46

MutPred

0.51

Gain of loop (P = 0.0312)

MVP

0.87

MPC

0.35

ClinPred

0.44

GERP RS

3.2

Varity_R

0.063

gMVP

0.59

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over