chr5-170259003-T-C

Variant names:

• chr5-170259003-T-C
• rs432621
• NM_005565.5:c.958-125A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005565.5(LCP2):​c.958-125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 648,196 control chromosomes in the GnomAD database, including 79,842 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (19583 hom., cov: 32)
  • Exomes 𝑓: 0.49 (60259 hom.)
• Consequence: LCP2 NM_005565.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.315
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-170259003-T-C is Benign according to our data. Variant chr5-170259003-T-C is described in ClinVar as Benign. ClinVar VariationId is 2688341.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.529 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.958-125A>G		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.958-125A>G		intron	N/A	ENSP00000046794.5	Q13094
	LCP2	ENST00000968849.1		c.967-125A>G		intron	N/A	ENSP00000638908.1
	LCP2	ENST00000968850.1		c.874-125A>G		intron	N/A	ENSP00000638909.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76885 AN: 151944 Hom.: 19569 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.505

GnomAD4 exome AF: 0.489 AC: 242600 AN: 496134 Hom.: 60259 AF XY: 0.487 AC XY: 129603 AN XY: 266376

African (AFR) AF: 0.537 AC: 7186 AN: 13380

American (AMR) AF: 0.541 AC: 12591 AN: 23264

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 8010 AN: 15540

East Asian (EAS) AF: 0.518 AC: 16094 AN: 31078

South Asian (SAS) AF: 0.462 AC: 23066 AN: 49964

European-Finnish (FIN) AF: 0.554 AC: 17114 AN: 30872

Middle Eastern (MID) AF: 0.546 AC: 1740 AN: 3184

European-Non Finnish (NFE) AF: 0.475 AC: 142974 AN: 301016

Other (OTH) AF: 0.497 AC: 13825 AN: 27836

GnomAD4 genome AF: 0.506 AC: 76941 AN: 152062 Hom.: 19583 Cov.: 32 AF XY: 0.512 AC XY: 38033 AN XY: 74348

African (AFR) AF: 0.535 AC: 22192 AN: 41468

American (AMR) AF: 0.523 AC: 7998 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1810 AN: 3470

East Asian (EAS) AF: 0.534 AC: 2762 AN: 5168

South Asian (SAS) AF: 0.461 AC: 2224 AN: 4826

European-Finnish (FIN) AF: 0.573 AC: 6059 AN: 10568

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32304 AN: 67962

Other (OTH) AF: 0.499 AC: 1055 AN: 2114

Alfa AF: 0.490 Hom.: 48778

Bravo AF: 0.503

Asia WGS AF: 0.462 AC: 1602 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.74
PhyloP100		0.32
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: rs432621; hg19: chr5-169686007; COSMIC: COSV50447860; COSMIC: COSV50447860;