5-170262515-G-A

Variant names:

• chr5-170262515-G-A
• rs2338871
• NM_005565.5:c.926+120C>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.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 rank	MANE	Protein	UniProt
LCP2	NM_005565.5	c.926+120C>T		intron_variant	Intron 13 of 20	ENST00000046794.10	NP_005556.1
LCP2	XM_047417171.1	c.695+120C>T		intron_variant	Intron 11 of 18		XP_047273127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCP2	ENST00000046794.10	c.926+120C>T		intron_variant	Intron 13 of 20	1	NM_005565.5	ENSP00000046794.5
LCP2	ENST00000521416.5	c.311+120C>T		intron_variant	Intron 5 of 12	2		ENSP00000428871.1
LCP2	ENST00000520344.1	c.227+120C>T		intron_variant	Intron 4 of 7	5		ENSP00000430391.1

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

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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;