rs3804254

Variant names:

• chr5-170258562-G-A
• rs3804254
• NM_005565.5:c.970+304C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005565.5(LCP2):​c.970+304C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 360,464 control chromosomes in the GnomAD database, including 44,261 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 0.50 (19205 hom., cov: 33)
  • Exomes 𝑓: 0.49 (25056 hom.)
• Consequence: LCP2 NM_005565.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687
• Publications: 5 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: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 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.970+304C>T		intron	N/A	NP_005556.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCP2	ENST00000046794.10	TSL:1 MANE Select	c.970+304C>T		intron	N/A	ENSP00000046794.5
	LCP2	ENST00000968849.1		c.979+304C>T		intron	N/A	ENSP00000638908.1
	LCP2	ENST00000968850.1		c.886+304C>T		intron	N/A	ENSP00000638909.1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76103 AN: 151998 Hom.: 19193 Cov.: 33

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.501

GnomAD4 exome AF: 0.485 AC: 101117 AN: 208348 Hom.: 25056 AF XY: 0.484 AC XY: 51578 AN XY: 106526

African (AFR) AF: 0.521 AC: 3680 AN: 7068

American (AMR) AF: 0.512 AC: 4301 AN: 8398

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 3923 AN: 7812

East Asian (EAS) AF: 0.498 AC: 9230 AN: 18528

South Asian (SAS) AF: 0.447 AC: 3343 AN: 7478

European-Finnish (FIN) AF: 0.555 AC: 7121 AN: 12824

Middle Eastern (MID) AF: 0.537 AC: 554 AN: 1032

European-Non Finnish (NFE) AF: 0.473 AC: 62212 AN: 131494

Other (OTH) AF: 0.492 AC: 6753 AN: 13714

GnomAD4 genome AF: 0.501 AC: 76155 AN: 152116 Hom.: 19205 Cov.: 33 AF XY: 0.507 AC XY: 37666 AN XY: 74356

African (AFR) AF: 0.526 AC: 21807 AN: 41484

American (AMR) AF: 0.512 AC: 7827 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1784 AN: 3472

East Asian (EAS) AF: 0.521 AC: 2700 AN: 5178

South Asian (SAS) AF: 0.458 AC: 2207 AN: 4822

European-Finnish (FIN) AF: 0.574 AC: 6066 AN: 10576

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32183 AN: 67984

Other (OTH) AF: 0.496 AC: 1047 AN: 2112

Alfa AF: 0.491 Hom.: 3255

Bravo AF: 0.496

Asia WGS AF: 0.455 AC: 1580 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.085
DANN	Benign	0.17
PhyloP100		-0.69
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: rs3804254; hg19: chr5-169685566; COSMIC: COSV50447853; COSMIC: COSV50447853;