5-170258159-C-T

Variant names:

• chr5-170258159-C-T
• rs315717
• NM_005565.5:c.978G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_005565.5(LCP2):​c.978G>A​(p.Gln326Gln) 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
• Publications: 26 publications found

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]

LCP2 Gene-Disease associations (from GenCC):

• immunodeficiency 81

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
LCP2	NM_005565.5	c.978G>A	p.Gln326Gln	synonymous_variant	Exon 16 of 21	ENST00000046794.10	NP_005556.1
LCP2	XM_047417171.1	c.747G>A	p.Gln249Gln	synonymous_variant	Exon 14 of 19		XP_047273127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCP2	ENST00000046794.10	c.978G>A	p.Gln326Gln	synonymous_variant	Exon 16 of 21	1	NM_005565.5	ENSP00000046794.5
LCP2	ENST00000521416.5	c.363G>A	p.Gln121Gln	synonymous_variant	Exon 8 of 13	2		ENSP00000428871.1
LCP2	ENST00000520344.1	c.279G>A	p.Gln93Gln	synonymous_variant	Exon 7 of 8	5		ENSP00000430391.1
LCP2	ENST00000523369.1	n.340G>A		non_coding_transcript_exon_variant	Exon 1 of 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

GnomAD2 exomes AF: 0.510 AC: 126939 AN: 249090 AF XY: 0.505

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 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

African (AFR) AF: 0.644 AC: 21535 AN: 33456

American (AMR) AF: 0.518 AC: 23163 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 13112 AN: 26124

East Asian (EAS) AF: 0.564 AC: 22399 AN: 39692

South Asian (SAS) AF: 0.462 AC: 39845 AN: 86238

European-Finnish (FIN) AF: 0.557 AC: 29738 AN: 53384

Middle Eastern (MID) AF: 0.541 AC: 3121 AN: 5768

European-Non Finnish (NFE) AF: 0.471 AC: 523755 AN: 1111032

Other (OTH) AF: 0.497 AC: 29999 AN: 60346

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

African (AFR) AF: 0.634 AC: 26268 AN: 41450

American (AMR) AF: 0.528 AC: 8078 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1761 AN: 3468

East Asian (EAS) AF: 0.578 AC: 2991 AN: 5172

South Asian (SAS) AF: 0.461 AC: 2219 AN: 4816

European-Finnish (FIN) AF: 0.574 AC: 6059 AN: 10548

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32234 AN: 67964

Other (OTH) AF: 0.519 AC: 1095 AN: 2108

Alfa AF: 0.496 Hom.: 77653

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

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 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
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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