5-170262600-G-C

Variant names:

• chr5-170262600-G-C
• rs395407
• NM_005565.5:c.926+35C>G

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 rank	MANE	Protein	UniProt
LCP2	NM_005565.5	c.926+35C>G		intron_variant	Intron 13 of 20	ENST00000046794.10	NP_005556.1
LCP2	XM_047417171.1	c.695+35C>G		intron_variant	Intron 11 of 18		XP_047273127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCP2	ENST00000046794.10	c.926+35C>G		intron_variant	Intron 13 of 20	1	NM_005565.5	ENSP00000046794.5
LCP2	ENST00000521416.5	c.311+35C>G		intron_variant	Intron 5 of 12	2		ENSP00000428871.1
LCP2	ENST00000520344.1	c.227+35C>G		intron_variant	Intron 4 of 7	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

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 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;