5-170253135-G-T

Variant names:

• chr5-170253135-G-T
• NM_005565.5:c.1229C>A

Variant summary

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

The NM_005565.5(LCP2):​c.1229C>A​(p.Ser410Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S410C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LCP2 NM_005565.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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=0.2139203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP2	NM_005565.5	c.1229C>A	p.Ser410Tyr	missense_variant	Exon 18 of 21	ENST00000046794.10	NP_005556.1
LCP2	XM_047417171.1	c.998C>A	p.Ser333Tyr	missense_variant	Exon 16 of 19		XP_047273127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCP2	ENST00000046794.10	c.1229C>A	p.Ser410Tyr	missense_variant	Exon 18 of 21	1	NM_005565.5	ENSP00000046794.5
LCP2	ENST00000521416.5	c.614C>A	p.Ser205Tyr	missense_variant	Exon 10 of 13	2		ENSP00000428871.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457650 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 724854

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Uncertain	0.63	D;T;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.0	M;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.3	N;.;N
REVEL	Benign	0.16
Sift	Uncertain	0.0080	D;.;D
Sift4G	Benign	0.21	T;T;T
Polyphen		0.84	P;.;P
Vest4		0.34
MutPred		0.26		Loss of glycosylation at S410 (P = 0.0247);Loss of glycosylation at S410 (P = 0.0247);.;
MVP		0.68
MPC		0.29
ClinPred		0.18	T
GERP RS		3.5
Varity_R		0.033
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-169680139;