dbSNP rs2271146: LCP2:c.255-35G>T (chr5-170275386-C-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.41

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 link	c.255-35G>T		intron_variant	Intron 4 of 20	ENST00000046794.10	NP_005556.1	Q13094
LCP2	XM_047417171.1 link	c.254+409G>T		intron_variant	Intron 4 of 18		XP_047273127.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LCP2	ENST00000046794.10 link	c.255-35G>T	intron_variant	Intron 4 of 20	1	NM_005565.5	ENSP00000046794.5	Q13094
LCP2	ENST00000519594.5 link	n.371-35G>T	intron_variant	Intron 4 of 6	2
LCP2	ENST00000522760.5 link	n.373-35G>T	intron_variant	Intron 4 of 5	2
LCP2	ENST00000522823.5 link	n.*239G>T	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.423

AC:

64282

AN:

151980

Hom.:

15046

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.439

AC:

109298

AN:

248802

Hom.:

26486

AF XY:

0.450

AC XY:

60746

AN XY:

134976

show subpopulations

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 SAS exome

AF:

0.429

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.:

AF XY:

0.498

AC XY:

361746

AN XY:

725804

show subpopulations

Gnomad4 AFR exome

AF:

0.256

Gnomad4 AMR exome

AF:

0.359

Gnomad4 ASJ exome

AF:

0.624

Gnomad4 EAS exome

AF:

0.0807

Gnomad4 SAS exome

AF:

0.434

Gnomad4 FIN exome

AF:

0.465

Gnomad4 NFE exome

AF:

0.530

Gnomad4 OTH exome

AF:

0.483

GnomAD4 genome

AF:

0.423

AC:

64290

AN:

152098

Hom.:

15048

Cov.:

AF XY:

0.418

AC XY:

31071

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.263

Gnomad4 AMR

AF:

0.438

Gnomad4 ASJ

AF:

0.616

Gnomad4 EAS

AF:

0.0739

Gnomad4 SAS

AF:

0.407

Gnomad4 FIN

AF:

0.457

Gnomad4 NFE

AF:

0.527

Gnomad4 OTH

AF:

0.466

Alfa

AF:

0.516

Hom.:

20605

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

LINK: link

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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over