rs315721

Variant names:

• chr5-170288034-A-G
• rs315721
• NM_005565.5:c.142-18T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005565.5(LCP2):​c.142-18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 1,611,306 control chromosomes in the GnomAD database, including 82,776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (8850 hom., cov: 32)
  • Exomes 𝑓: 0.32 (73926 hom.)
• Consequence: LCP2 NM_005565.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0870
• Publications: 16 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-170288034-A-G is Benign according to our data. Variant chr5-170288034-A-G is described in ClinVar as Benign. ClinVar VariationId is 2688081.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP2	NM_005565.5	c.142-18T>C		intron_variant	Intron 2 of 20	ENST00000046794.10	NP_005556.1
LCP2	XM_047417171.1	c.142-18T>C		intron_variant	Intron 2 of 18		XP_047273127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCP2	ENST00000046794.10	c.142-18T>C		intron_variant	Intron 2 of 20	1	NM_005565.5	ENSP00000046794.5

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51403 AN: 151858 Hom.: 8837 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.344

GnomAD2 exomes AF: 0.335 AC: 83375 AN: 248914 AF XY: 0.335

Gnomad AFR exome AF: 0.376

Gnomad AMR exome AF: 0.377

Gnomad ASJ exome AF: 0.353

Gnomad EAS exome AF: 0.342

Gnomad FIN exome AF: 0.281

Gnomad NFE exome AF: 0.316

Gnomad OTH exome AF: 0.327

GnomAD4 exome AF: 0.315 AC: 460290 AN: 1459330 Hom.: 73926 Cov.: 32 AF XY: 0.317 AC XY: 230289 AN XY: 726048

African (AFR) AF: 0.381 AC: 12717 AN: 33408

American (AMR) AF: 0.370 AC: 16554 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 9189 AN: 26124

East Asian (EAS) AF: 0.411 AC: 16313 AN: 39688

South Asian (SAS) AF: 0.365 AC: 31419 AN: 86188

European-Finnish (FIN) AF: 0.289 AC: 15425 AN: 53380

Middle Eastern (MID) AF: 0.396 AC: 2277 AN: 5756

European-Non Finnish (NFE) AF: 0.303 AC: 336794 AN: 1109818

Other (OTH) AF: 0.325 AC: 19602 AN: 60284

GnomAD4 genome AF: 0.339 AC: 51463 AN: 151976 Hom.: 8850 Cov.: 32 AF XY: 0.337 AC XY: 25058 AN XY: 74264

African (AFR) AF: 0.380 AC: 15760 AN: 41442

American (AMR) AF: 0.341 AC: 5212 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1208 AN: 3464

East Asian (EAS) AF: 0.364 AC: 1878 AN: 5162

South Asian (SAS) AF: 0.382 AC: 1845 AN: 4826

European-Finnish (FIN) AF: 0.294 AC: 3103 AN: 10538

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21281 AN: 67954

Other (OTH) AF: 0.341 AC: 721 AN: 2112

Alfa AF: 0.327 Hom.: 15760

Bravo AF: 0.341

Asia WGS AF: 0.350 AC: 1216 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 58% of patients studied by a panel of primary immunodeficiencies. Number of patients: 55. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.97
DANN	Benign	0.65
PhyloP100		0.087
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs315721; hg19: chr5-169715038; COSMIC: COSV50447905;