5-170262515-G-A

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.926+120C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 686,120 control chromosomes in the GnomAD database, including 14,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2597 hom., cov: 32)
  • Exomes 𝑓: 0.21 (11930 hom.)
• Consequence: LCP2 NM_005565.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.768

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=-0.96).
• BP6: Variant 5-170262515-G-A is Benign according to our data. Variant chr5-170262515-G-A is described in ClinVar as [Benign]. Clinvar id is 2688247.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCP2	NM_005565.5	c.926+120C>T		intron_variant		ENST00000046794.10
LCP2	XM_047417171.1	c.695+120C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCP2	ENST00000046794.10	c.926+120C>T		intron_variant		1	NM_005565.5	P1
LCP2	ENST00000520344.1	c.227+120C>T		intron_variant		5
LCP2	ENST00000521416.5	c.311+120C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25775 AN: 152052 Hom.: 2593 Cov.: 32

Gnomad AFR AF: 0.0606

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.205 AC: 109461 AN: 533950 Hom.: 11930 AF XY: 0.204 AC XY: 57059 AN XY: 280184

Gnomad4 AFR exome AF: 0.0605

Gnomad4 AMR exome AF: 0.275

Gnomad4 ASJ exome AF: 0.141

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.209

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.201

GnomAD4 genome AF: 0.169 AC: 25790 AN: 152170 Hom.: 2597 Cov.: 32 AF XY: 0.173 AC XY: 12861 AN XY: 74374

Gnomad4 AFR AF: 0.0606

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.164

Alfa AF: 0.195 Hom.: 4081

Bravo AF: 0.170

Asia WGS AF: 0.247 AC: 856 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 31% of patients studied by a panel of primary immunodeficiencies. Number of patients: 29. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.14
Dann	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2338871; hg19: chr5-169689519;