rs315717

Positions:

• chr5-170258159-C-G
• chr5-170258159-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005565.5(LCP2):​c.978G>C​(p.Gln326His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: LCP2 NM_005565.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.30

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11984837).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCP2	NM_005565.5	c.978G>C	p.Gln326His	missense_variant	16/21	ENST00000046794.10	NP_005556.1
LCP2	XM_047417171.1	c.747G>C	p.Gln249His	missense_variant	14/19		XP_047273127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCP2	ENST00000046794.10	c.978G>C	p.Gln326His	missense_variant	16/21	1	NM_005565.5	ENSP00000046794	P1
LCP2	ENST00000521416.5	c.363G>C	p.Gln121His	missense_variant	8/13	2		ENSP00000428871
LCP2	ENST00000520344.1	c.279G>C	p.Gln93His	missense_variant	7/8	5		ENSP00000430391
LCP2	ENST00000523369.1	n.340G>C		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151954 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome Cov.: 40

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151954 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74214

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.14
DANN	Benign	0.94
DEOGEN2	Uncertain	0.47	T;T;T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.80	T;T;T;T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Uncertain	0.084	D
MutationAssessor	Uncertain	2.2	M;.;.;.
MutationTaster	Benign	0.99	P;P
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.4	N;.;N;D
REVEL	Benign	0.18
Sift	Uncertain	0.021	D;.;T;D
Sift4G	Benign	0.17	T;T;T;T
Polyphen		1.0	D;.;D;.
Vest4		0.18
MutPred		0.28		Loss of solvent accessibility (P = 0.0238);Loss of solvent accessibility (P = 0.0238);.;.;
MVP		0.63
MPC		0.58
ClinPred		0.55	D
GERP RS		-11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.063
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs315717; hg19: chr5-169685163;