5-170262600-G-C

Position:

• chr5-170262600-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005565.5(LCP2):​c.926+35C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 1,522,876 control chromosomes in the GnomAD database, including 575,165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.89 (60647 hom., cov: 34)
  • Exomes 𝑓: 0.87 (514518 hom.)
• Consequence: LCP2 NM_005565.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.324

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-170262600-G-C is Benign according to our data. Variant chr5-170262600-G-C is described in ClinVar as [Benign]. Clinvar id is 2688075.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCP2	NM_005565.5	c.926+35C>G		intron_variant		ENST00000046794.10	NP_005556.1
LCP2	XM_047417171.1	c.695+35C>G		intron_variant			XP_047273127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCP2	ENST00000046794.10	c.926+35C>G		intron_variant		1	NM_005565.5	ENSP00000046794.5
LCP2	ENST00000521416.5	c.311+35C>G		intron_variant		2		ENSP00000428871.1
LCP2	ENST00000520344.1	c.227+35C>G		intron_variant		5		ENSP00000430391.1

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135630 AN: 152182 Hom.: 60602 Cov.: 34

Gnomad AFR AF: 0.961

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.898

GnomAD3 exomes AF: 0.883 AC: 192264 AN: 217696 Hom.: 85106 AF XY: 0.886 AC XY: 104021 AN XY: 117456

Gnomad AFR exome AF: 0.963

Gnomad AMR exome AF: 0.890

Gnomad ASJ exome AF: 0.857

Gnomad EAS exome AF: 0.938

Gnomad SAS exome AF: 0.946

Gnomad FIN exome AF: 0.832

Gnomad NFE exome AF: 0.857

Gnomad OTH exome AF: 0.872

GnomAD4 exome AF: 0.866 AC: 1186590 AN: 1370576 Hom.: 514518 Cov.: 20 AF XY: 0.868 AC XY: 593851 AN XY: 684028

Gnomad4 AFR exome AF: 0.969

Gnomad4 AMR exome AF: 0.890

Gnomad4 ASJ exome AF: 0.856

Gnomad4 EAS exome AF: 0.932

Gnomad4 SAS exome AF: 0.944

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.854

Gnomad4 OTH exome AF: 0.877

GnomAD4 genome AF: 0.891 AC: 135733 AN: 152300 Hom.: 60647 Cov.: 34 AF XY: 0.892 AC XY: 66410 AN XY: 74464

Gnomad4 AFR AF: 0.961

Gnomad4 AMR AF: 0.876

Gnomad4 ASJ AF: 0.854

Gnomad4 EAS AF: 0.943

Gnomad4 SAS AF: 0.951

Gnomad4 FIN AF: 0.837

Gnomad4 NFE AF: 0.854

Gnomad4 OTH AF: 0.899

Alfa AF: 0.854 Hom.: 6001

Bravo AF: 0.898

Asia WGS AF: 0.946 AC: 3289 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 100% of patients studied by a panel of primary immunodeficiencies. Number of patients: 95. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.43

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

Other links and lift over

dbSNP: rs395407; hg19: chr5-169689604;