NM_005565.5:c.523+16C>T

Variant names:

• chr5-170270703-G-A
• rs315745
• NM_005565.5:c.523+16C>T

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.523+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 1,540,650 control chromosomes in the GnomAD database, including 207,919 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (20844 hom., cov: 32)
  • Exomes 𝑓: 0.51 (187075 hom.)
• Consequence: LCP2 NM_005565.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.558
• Publications: 8 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)

ENSG00000300307 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 5-170270703-G-A is Benign according to our data. Variant chr5-170270703-G-A is described in ClinVar as Benign. ClinVar VariationId is 2687975.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP2	NM_005565.5	c.523+16C>T		intron_variant	Intron 7 of 20	ENST00000046794.10	NP_005556.1
LCP2	XM_047417171.1	c.293-2221C>T		intron_variant	Intron 5 of 18		XP_047273127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCP2	ENST00000046794.10	c.523+16C>T		intron_variant	Intron 7 of 20	1	NM_005565.5	ENSP00000046794.5
LCP2	ENST00000519594.5	n.655C>T		non_coding_transcript_exon_variant	Exon 7 of 7	2
ENSG00000300307	ENST00000770716.1	n.-240G>A		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78625 AN: 151910 Hom.: 20804 Cov.: 32

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.478

GnomAD2 exomes AF: 0.540 AC: 104138 AN: 192964 AF XY: 0.533

Gnomad AFR exome AF: 0.500

Gnomad AMR exome AF: 0.644

Gnomad ASJ exome AF: 0.359

Gnomad EAS exome AF: 0.841

Gnomad FIN exome AF: 0.509

Gnomad NFE exome AF: 0.500

Gnomad OTH exome AF: 0.496

GnomAD4 exome AF: 0.514 AC: 713537 AN: 1388622 Hom.: 187075 Cov.: 35 AF XY: 0.512 AC XY: 351604 AN XY: 686508

African (AFR) AF: 0.499 AC: 14771 AN: 29604

American (AMR) AF: 0.627 AC: 19620 AN: 31284

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 8428 AN: 23240

East Asian (EAS) AF: 0.864 AC: 31167 AN: 36064

South Asian (SAS) AF: 0.531 AC: 39553 AN: 74440

European-Finnish (FIN) AF: 0.519 AC: 27080 AN: 52128

Middle Eastern (MID) AF: 0.417 AC: 1908 AN: 4580

European-Non Finnish (NFE) AF: 0.501 AC: 541542 AN: 1079898

Other (OTH) AF: 0.514 AC: 29468 AN: 57384

GnomAD4 genome AF: 0.518 AC: 78716 AN: 152028 Hom.: 20844 Cov.: 32 AF XY: 0.522 AC XY: 38814 AN XY: 74286

African (AFR) AF: 0.501 AC: 20741 AN: 41432

American (AMR) AF: 0.554 AC: 8478 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1271 AN: 3472

East Asian (EAS) AF: 0.849 AC: 4381 AN: 5160

South Asian (SAS) AF: 0.552 AC: 2655 AN: 4812

European-Finnish (FIN) AF: 0.509 AC: 5373 AN: 10562

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.502 AC: 34128 AN: 67978

Other (OTH) AF: 0.485 AC: 1025 AN: 2114

Alfa AF: 0.494 Hom.: 5944

Bravo AF: 0.523

Asia WGS AF: 0.716 AC: 2490 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 82% of patients studied by a panel of primary immunodeficiencies. Number of patients: 78. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.35
DANN	Benign	0.42
PhyloP100		-0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs315745; hg19: chr5-169697707; COSMIC: COSV50446678; COSMIC: COSV50446678;