LCP2 p.Gln326His

Variant names:

• chr5-170258159-C-A
• NM_005565.5:c.978G>T
• LCP2 p.Gln326His

Your query was ambiguous. Multiple possible variants found:

• chr5-170258159-C-A
• chr5-170258159-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005565.5(LCP2):​c.978G>T​(p.Gln326His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q326Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LCP2 NM_005565.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.30
• Publications: 0 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, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11984137).

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.978G>T	p.Gln326His	missense	Exon 16 of 21	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.978G>T	p.Gln326His	missense	Exon 16 of 21	ENSP00000046794.5	Q13094
	LCP2	ENST00000968849.1		c.987G>T	p.Gln329His	missense	Exon 16 of 21	ENSP00000638908.1
	LCP2	ENST00000968850.1		c.894G>T	p.Gln298His	missense	Exon 15 of 20	ENSP00000638909.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.12
DANN	Benign	0.93
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.12	T
MetaSVM	Uncertain	0.084	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		-3.3
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.18
Sift	Uncertain	0.021	D
Sift4G	Benign	0.17	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.063
gMVP		0.52
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-169685163;