NM_005565.5:c.255-35G>T

Variant names:

• chr5-170275386-C-A
• rs2271146
• NM_005565.5:c.255-35G>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.255-35G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,610,858 control chromosomes in the GnomAD database, including 202,715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (15048 hom., cov: 32)
  • Exomes 𝑓: 0.50 (187667 hom.)
• Consequence: LCP2 NM_005565.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.41
• Publications: 11 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=-0.92).
• BP6: Variant 5-170275386-C-A is Benign according to our data. Variant chr5-170275386-C-A is described in ClinVar as Benign. ClinVar VariationId is 2688035.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP2	NM_005565.5	c.255-35G>T		intron_variant	Intron 4 of 20	ENST00000046794.10	NP_005556.1
LCP2	XM_047417171.1	c.254+409G>T		intron_variant	Intron 4 of 18		XP_047273127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCP2	ENST00000046794.10	c.255-35G>T		intron_variant	Intron 4 of 20	1	NM_005565.5	ENSP00000046794.5
LCP2	ENST00000519594.5	n.371-35G>T		intron_variant	Intron 4 of 6	2
LCP2	ENST00000522760.5	n.373-35G>T		intron_variant	Intron 4 of 5	2
LCP2	ENST00000522823.5	n.*239G>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64282 AN: 151980 Hom.: 15046 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.0745

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.472

GnomAD2 exomes AF: 0.439 AC: 109298 AN: 248802 AF XY: 0.450

Gnomad AFR exome AF: 0.254

Gnomad AMR exome AF: 0.347

Gnomad ASJ exome AF: 0.623

Gnomad EAS exome AF: 0.0811

Gnomad FIN exome AF: 0.465

Gnomad NFE exome AF: 0.528

Gnomad OTH exome AF: 0.501

GnomAD4 exome AF: 0.498 AC: 726355 AN: 1458760 Hom.: 187667 Cov.: 33 AF XY: 0.498 AC XY: 361746 AN XY: 725804

African (AFR) AF: 0.256 AC: 8569 AN: 33438

American (AMR) AF: 0.359 AC: 16040 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 16293 AN: 26120

East Asian (EAS) AF: 0.0807 AC: 3204 AN: 39694

South Asian (SAS) AF: 0.434 AC: 37376 AN: 86190

European-Finnish (FIN) AF: 0.465 AC: 24808 AN: 53342

Middle Eastern (MID) AF: 0.622 AC: 3555 AN: 5712

European-Non Finnish (NFE) AF: 0.530 AC: 587385 AN: 1109306

Other (OTH) AF: 0.483 AC: 29125 AN: 60258

GnomAD4 genome AF: 0.423 AC: 64290 AN: 152098 Hom.: 15048 Cov.: 32 AF XY: 0.418 AC XY: 31071 AN XY: 74342

African (AFR) AF: 0.263 AC: 10913 AN: 41476

American (AMR) AF: 0.438 AC: 6692 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2140 AN: 3472

East Asian (EAS) AF: 0.0739 AC: 383 AN: 5180

South Asian (SAS) AF: 0.407 AC: 1964 AN: 4824

European-Finnish (FIN) AF: 0.457 AC: 4833 AN: 10564

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35821 AN: 67974

Other (OTH) AF: 0.466 AC: 983 AN: 2110

Alfa AF: 0.496 Hom.: 28519

Bravo AF: 0.410

Asia WGS AF: 0.218 AC: 761 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 66% of patients studied by a panel of primary immunodeficiencies. Number of patients: 63. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.036
DANN	Benign	0.55
PhyloP100		-1.4
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: rs2271146; hg19: chr5-169702390; COSMIC: COSV50452228; COSMIC: COSV50452228;