5-170297320-A-T

Position:

• chr5-170297320-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005565.5(LCP2):​c.78+214T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,040 control chromosomes in the GnomAD database, including 12,659 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (12659 hom., cov: 32)
• Consequence: LCP2 NM_005565.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCP2	NM_005565.5	c.78+214T>A		intron_variant		ENST00000046794.10
LCP2	XM_047417171.1	c.78+214T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCP2	ENST00000046794.10	c.78+214T>A		intron_variant		1	NM_005565.5	P1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61671 AN: 151922 Hom.: 12659 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.419

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.406 AC: 61686 AN: 152040 Hom.: 12659 Cov.: 32 AF XY: 0.403 AC XY: 29929 AN XY: 74304

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.418

Alfa AF: 0.416 Hom.: 1636

Bravo AF: 0.404

Asia WGS AF: 0.300 AC: 1044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.68

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: rs315730; hg19: chr5-169724324; COSMIC: COSV50452599;