5-170297320-A-T

Variant names:

• chr5-170297320-A-T
• rs315730
• NM_005565.5:c.78+214T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 81

  Inheritance: AR, Unknown Classification: DEFINITIVE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005565.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCP2	NM_005565.5	MANE Select	c.78+214T>A		intron	N/A	NP_005556.1	Q13094

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCP2	ENST00000046794.10	TSL:1 MANE Select	c.78+214T>A		intron	N/A	ENSP00000046794.5	Q13094
	LCP2	ENST00000968849.1		c.78+214T>A		intron	N/A	ENSP00000638908.1
	LCP2	ENST00000968850.1		c.78+214T>A		intron	N/A	ENSP00000638909.1

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

African (AFR) AF: 0.353 AC: 14620 AN: 41458

American (AMR) AF: 0.429 AC: 6566 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1543 AN: 3470

East Asian (EAS) AF: 0.277 AC: 1432 AN: 5170

South Asian (SAS) AF: 0.279 AC: 1345 AN: 4826

European-Finnish (FIN) AF: 0.450 AC: 4760 AN: 10570

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29988 AN: 67940

Other (OTH) AF: 0.418 AC: 884 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.68
PhyloP100		-0.14
PromoterAI		0.036	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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