5-170258159-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_005565.5(LCP2):c.978G>A(p.Gln326=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,612,780 control chromosomes in the GnomAD database, including 194,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.53 (22216 hom., cov: 32)
  • Exomes 𝑓: 0.48 (172473 hom.)
• Consequence: LCP2 NM_005565.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.30

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-170258159-C-T is Benign according to our data. Variant chr5-170258159-C-T is described in ClinVar as [Benign]. Clinvar id is 2687970.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.3 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCP2	NM_005565.5	c.978G>A	p.Gln326=	synonymous_variant	16/21	ENST00000046794.10
LCP2	XM_047417171.1	c.747G>A	p.Gln249=	synonymous_variant	14/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCP2	ENST00000046794.10	c.978G>A	p.Gln326=	synonymous_variant	16/21	1	NM_005565.5	P1
LCP2	ENST00000521416.5	c.363G>A	p.Gln121=	synonymous_variant	8/13	2
LCP2	ENST00000520344.1	c.279G>A	p.Gln93=	synonymous_variant	7/8	5
LCP2	ENST00000523369.1	n.340G>A		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81183 AN: 151900 Hom.: 22201 Cov.: 32

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.525

GnomAD3 exomes AF: 0.510 AC: 126939 AN: 249090 Hom.: 32892 AF XY: 0.505 AC XY: 68277 AN XY: 135162

Gnomad AFR exome AF: 0.638

Gnomad AMR exome AF: 0.512

Gnomad ASJ exome AF: 0.509

Gnomad EAS exome AF: 0.593

Gnomad SAS exome AF: 0.465

Gnomad FIN exome AF: 0.559

Gnomad NFE exome AF: 0.481

Gnomad OTH exome AF: 0.511

GnomAD4 exome AF: 0.484 AC: 706667 AN: 1460762 Hom.: 172473 Cov.: 40 AF XY: 0.483 AC XY: 350982 AN XY: 726756

Gnomad4 AFR exome AF: 0.644

Gnomad4 AMR exome AF: 0.518

Gnomad4 ASJ exome AF: 0.502

Gnomad4 EAS exome AF: 0.564

Gnomad4 SAS exome AF: 0.462

Gnomad4 FIN exome AF: 0.557

Gnomad4 NFE exome AF: 0.471

Gnomad4 OTH exome AF: 0.497

GnomAD4 genome AF: 0.534 AC: 81239 AN: 152018 Hom.: 22216 Cov.: 32 AF XY: 0.540 AC XY: 40118 AN XY: 74310

Gnomad4 AFR AF: 0.634

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.578

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.519

Alfa AF: 0.491 Hom.: 38460

Bravo AF: 0.535

Asia WGS AF: 0.485 AC: 1688 AN: 3478

EpiCase AF: 0.478

EpiControl AF: 0.483

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 84% of patients studied by a panel of primary immunodeficiencies. Number of patients: 80. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.073
Dann	Benign	0.38

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: rs315717; hg19: chr5-169685163; COSMIC: COSV50446810;