rs34192428

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005565.5(LCP2):c.1229C>G(p.Ser410Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0162 in 1,609,648 control chromosomes in the GnomAD database, including 263 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S410P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.012 ( 18 hom., cov: 33)

Exomes 𝑓: 0.017 ( 245 hom. )

Consequence

LCP2
NM_005565.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.04

Publications

13 publications found

Variant links:

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

LCP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0049465597).

BP6

Variant 5-170253135-G-C is Benign according to our data. Variant chr5-170253135-G-C is described in ClinVar as Benign. ClinVar VariationId is 2656067.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0117 (1775/152284) while in subpopulation NFE AF = 0.0176 (1200/68022). AF 95% confidence interval is 0.0168. There are 18 homozygotes in GnomAd4. There are 806 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 18 AR,Unknown gene

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.1229C>G	p.Ser410Cys	missense	Exon 18 of 21	NP_005556.1	Q13094

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LCP2	ENST00000046794.10	TSL:1 MANE Select	c.1229C>G	p.Ser410Cys	missense	Exon 18 of 21	ENSP00000046794.5	Q13094
LCP2	ENST00000968849.1		c.1238C>G	p.Ser413Cys	missense	Exon 18 of 21	ENSP00000638908.1
LCP2	ENST00000968850.1		c.1145C>G	p.Ser382Cys	missense	Exon 17 of 20	ENSP00000638909.1

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1775

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00285

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00913

Gnomad FIN

AF:

0.0149

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0176

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.0122

AC:

2980

AN:

244384

AF XY:

0.0122

show subpopulations

Gnomad AFR exome

AF:

0.00362

Gnomad AMR exome

AF:

0.00796

Gnomad ASJ exome

AF:

0.0142

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0129

Gnomad NFE exome

AF:

0.0171

Gnomad OTH exome

AF:

0.0127

GnomAD4 exome

AF:

0.0167

AC:

24363

AN:

1457364

Hom.:

245

Cov.:

AF XY:

0.0165

AC XY:

11936

AN XY:

724726

show subpopulations

African (AFR)

AF:

0.00278

AC:

AN:

33414

American (AMR)

AF:

0.00930

AC:

413

AN:

44430

Ashkenazi Jewish (ASJ)

AF:

0.0143

AC:

373

AN:

26064

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.00916

AC:

782

AN:

85360

European-Finnish (FIN)

AF:

0.0136

AC:

723

AN:

53224

Middle Eastern (MID)

AF:

0.0106

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0189

AC:

20990

AN:

1109244

Other (OTH)

AF:

0.0154

AC:

928

AN:

60210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

984

1968

2953

3937

4921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

804

1608

2412

3216

4020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0117

AC:

1775

AN:

152284

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

806

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00284

AC:

118

AN:

41562

American (AMR)

AF:

0.0122

AC:

186

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0130

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00914

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0149

AC:

158

AN:

10608

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0176

AC:

1200

AN:

68022

Other (OTH)

AF:

0.0104

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

190

286

381

476

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0161

Hom.:

Bravo

AF:

0.0112

TwinsUK

AF:

0.0216

AC:

ALSPAC

AF:

0.0202

AC:

ESP6500AA

AF:

0.00385

AC:

ESP6500EA

AF:

0.0201

AC:

164

ExAC

AF:

0.0118

AC:

1422

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.64

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.58

MetaRNN

Benign

0.0049

MetaSVM

Uncertain

-0.10

MutationAssessor

Uncertain

2.0

PhyloP100

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.0

REVEL

Benign

0.19

Sift

Uncertain

0.010

Sift4G

Benign

0.069

Polyphen

1.0

Vest4

0.16

MPC

0.38

ClinPred

0.014

GERP RS

3.5

Varity_R

0.049

gMVP

0.45

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over