Genetic Variant LCP2:p.Gln326Gln (chr5-170258159-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.30

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 link	c.978G>A	p.Gln326Gln	synonymous_variant	Exon 16 of 21	ENST00000046794.10	NP_005556.1	Q13094
LCP2	XM_047417171.1 link	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	UniProt
LCP2	ENST00000046794.10 link	c.978G>A	p.Gln326Gln	synonymous_variant	Exon 16 of 21	1	NM_005565.5	ENSP00000046794.5	Q13094
LCP2	ENST00000521416.5 link	c.363G>A	p.Gln121Gln	synonymous_variant	Exon 8 of 13	2		ENSP00000428871.1	E7ESF6
LCP2	ENST00000520344.1 link	c.279G>A	p.Gln93Gln	synonymous_variant	Exon 7 of 8	5		ENSP00000430391.1	E5RKA2
LCP2	ENST00000523369.1 link	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.:

show subpopulations

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

GnomAD3 exomes

AF:

0.510

AC:

126939

AN:

249090

Hom.:

32892

AF XY:

0.505

AC XY:

68277

AN XY:

135162

show subpopulations

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 SAS exome

AF:

0.465

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.:

AF XY:

0.483

AC XY:

350982

AN XY:

726756

show subpopulations

Gnomad4 AFR exome

AF:

0.644

Gnomad4 AMR exome

AF:

0.518

Gnomad4 ASJ exome

AF:

0.502

Gnomad4 EAS exome

AF:

0.564

Gnomad4 SAS exome

AF:

0.462

Gnomad4 FIN exome

AF:

0.557

Gnomad4 NFE exome

AF:

0.471

Gnomad4 OTH exome

AF:

0.497

GnomAD4 genome

AF:

0.534

AC:

81239

AN:

152018

Hom.:

22216

Cov.:

AF XY:

0.540

AC XY:

40118

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.634

Gnomad4 AMR

AF:

0.528

Gnomad4 ASJ

AF:

0.508

Gnomad4 EAS

AF:

0.578

Gnomad4 SAS

AF:

0.461

Gnomad4 FIN

AF:

0.574

Gnomad4 NFE

AF:

0.474

Gnomad4 OTH

AF:

0.519

Alfa

AF:

0.491

Hom.:

38460

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

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 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

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

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