rs315745

chr5-170270703-G-Achr5-170270703-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005565.5(LCP2):c.523+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 1,540,650 control chromosomes in the GnomAD database, including 207,919 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (20844 hom., cov: 32)
  • Exomes 𝑓: 0.51 (187075 hom.)
• Consequence: LCP2 NM_005565.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.558

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 5-170270703-G-A is Benign according to our data. Variant chr5-170270703-G-A is described in ClinVar as [Benign]. Clinvar id is 2687975.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCP2	NM_005565.5	c.523+16C>T		intron_variant		ENST00000046794.10
LCP2	XM_047417171.1	c.293-2221C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCP2	ENST00000046794.10	c.523+16C>T		intron_variant		1	NM_005565.5	P1
LCP2	ENST00000519594.5	n.655C>T		non_coding_transcript_exon_variant	7/7	2

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78625 AN: 151910 Hom.: 20804 Cov.: 32

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.478

GnomAD3 exomes AF: 0.540 AC: 104138 AN: 192964 Hom.: 29317 AF XY: 0.533 AC XY: 56194 AN XY: 105450

Gnomad AFR exome AF: 0.500

Gnomad AMR exome AF: 0.644

Gnomad ASJ exome AF: 0.359

Gnomad EAS exome AF: 0.841

Gnomad SAS exome AF: 0.542

Gnomad FIN exome AF: 0.509

Gnomad NFE exome AF: 0.500

Gnomad OTH exome AF: 0.496

GnomAD4 exome AF: 0.514 AC: 713537 AN: 1388622 Hom.: 187075 Cov.: 35 AF XY: 0.512 AC XY: 351604 AN XY: 686508

Gnomad4 AFR exome AF: 0.499

Gnomad4 AMR exome AF: 0.627

Gnomad4 ASJ exome AF: 0.363

Gnomad4 EAS exome AF: 0.864

Gnomad4 SAS exome AF: 0.531

Gnomad4 FIN exome AF: 0.519

Gnomad4 NFE exome AF: 0.501

Gnomad4 OTH exome AF: 0.514

GnomAD4 genome AF: 0.518 AC: 78716 AN: 152028 Hom.: 20844 Cov.: 32 AF XY: 0.522 AC XY: 38814 AN XY: 74286

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.849

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.485

Alfa AF: 0.494 Hom.: 5944

Bravo AF: 0.523

Asia WGS AF: 0.716 AC: 2490 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 82% of patients studied by a panel of primary immunodeficiencies. Number of patients: 78. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.35
Dann	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs315745; hg19: chr5-169697707; COSMIC: COSV50446678; COSMIC: COSV50446678;