5-170262647-G-C

Position:

• chr5-170262647-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005565.5(LCP2):​c.914C>G​(p.Pro305Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LCP2 NM_005565.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.78

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32389534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCP2	NM_005565.5	c.914C>G	p.Pro305Arg	missense_variant	13/21	ENST00000046794.10
LCP2	XM_047417171.1	c.683C>G	p.Pro228Arg	missense_variant	11/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCP2	ENST00000046794.10	c.914C>G	p.Pro305Arg	missense_variant	13/21	1	NM_005565.5	P1
LCP2	ENST00000521416.5	c.299C>G	p.Pro100Arg	missense_variant	5/13	2
LCP2	ENST00000520344.1	c.215C>G	p.Pro72Arg	missense_variant	4/8	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2022

The c.914C>G (p.P305R) alteration is located in exon 13 (coding exon 13) of the LCP2 gene. This alteration results from a C to G substitution at nucleotide position 914, causing the proline (P) at amino acid position 305 to be replaced by an arginine (R). 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	0.20
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D;T;T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	T;T;T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.2	M;.;.;.
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.8	N;.;N;D
REVEL	Benign	0.17
Sift	Uncertain	0.0070	D;.;D;D
Sift4G	Benign	0.65	T;T;T;D
Polyphen		1.0	D;.;D;.
Vest4		0.36
MutPred		0.29		Gain of MoRF binding (P = 0.0027);Gain of MoRF binding (P = 0.0027);.;.;
MVP		0.68
MPC		0.73
ClinPred		0.90	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.081
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr5-169689651;