rs2338872

Positions:

• chr5-170265550-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005565.5(LCP2):​c.772+1258C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,072 control chromosomes in the GnomAD database, including 33,514 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (33514 hom., cov: 32)
• Consequence: LCP2 NM_005565.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCP2	NM_005565.5	c.772+1258C>T		intron_variant		ENST00000046794.10
LCP2	XM_047417171.1	c.541+1258C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCP2	ENST00000046794.10	c.772+1258C>T		intron_variant		1	NM_005565.5	P1
LCP2	ENST00000520344.1	c.73+1459C>T		intron_variant		5
LCP2	ENST00000521416.5	c.157+1258C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99719 AN: 151954 Hom.: 33461 Cov.: 32

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.624

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.656 AC: 99831 AN: 152072 Hom.: 33514 Cov.: 32 AF XY: 0.663 AC XY: 49247 AN XY: 74332

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.957

Gnomad4 SAS AF: 0.687

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.629

Alfa AF: 0.599 Hom.: 37793

Bravo AF: 0.666

Asia WGS AF: 0.839 AC: 2917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.018
DANN	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs2338872; hg19: chr5-169692554;