rs2271146

chr5-170275386-C-Achr5-170275386-C-T

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.255-35G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,610,858 control chromosomes in the GnomAD database, including 202,715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (15048 hom., cov: 32)
  • Exomes 𝑓: 0.50 (187667 hom.)
• Consequence: LCP2 NM_005565.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.41

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=-0.92).
• BP6: Variant 5-170275386-C-A is Benign according to our data. Variant chr5-170275386-C-A is described in ClinVar as [Benign]. Clinvar id is 2688035.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCP2	NM_005565.5	c.255-35G>T		intron_variant		ENST00000046794.10
LCP2	XM_047417171.1	c.254+409G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCP2	ENST00000046794.10	c.255-35G>T		intron_variant		1	NM_005565.5	P1
LCP2	ENST00000519594.5	n.371-35G>T		intron_variant, non_coding_transcript_variant		2
LCP2	ENST00000522760.5	n.373-35G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64282 AN: 151980 Hom.: 15046 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.0745

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.472

GnomAD3 exomes AF: 0.439 AC: 109298 AN: 248802 Hom.: 26486 AF XY: 0.450 AC XY: 60746 AN XY: 134976

Gnomad AFR exome AF: 0.254

Gnomad AMR exome AF: 0.347

Gnomad ASJ exome AF: 0.623

Gnomad EAS exome AF: 0.0811

Gnomad SAS exome AF: 0.429

Gnomad FIN exome AF: 0.465

Gnomad NFE exome AF: 0.528

Gnomad OTH exome AF: 0.501

GnomAD4 exome AF: 0.498 AC: 726355 AN: 1458760 Hom.: 187667 Cov.: 33 AF XY: 0.498 AC XY: 361746 AN XY: 725804

Gnomad4 AFR exome AF: 0.256

Gnomad4 AMR exome AF: 0.359

Gnomad4 ASJ exome AF: 0.624

Gnomad4 EAS exome AF: 0.0807

Gnomad4 SAS exome AF: 0.434

Gnomad4 FIN exome AF: 0.465

Gnomad4 NFE exome AF: 0.530

Gnomad4 OTH exome AF: 0.483

GnomAD4 genome AF: 0.423 AC: 64290 AN: 152098 Hom.: 15048 Cov.: 32 AF XY: 0.418 AC XY: 31071 AN XY: 74342

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.0739

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.466

Alfa AF: 0.516 Hom.: 20605

Bravo AF: 0.410

Asia WGS AF: 0.218 AC: 761 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 66% of patients studied by a panel of primary immunodeficiencies. Number of patients: 63. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.036
Dann	Benign	0.55

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: rs2271146; hg19: chr5-169702390; COSMIC: COSV50452228; COSMIC: COSV50452228;