dbSNP rs187889192: LCP2:p.Tyr522His (chr5-170248735-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005565.5(LCP2):c.1564T>C(p.Tyr522His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00328 in 1,610,636 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 13 hom. )

Consequence

LCP2
NM_005565.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.08

Publications

5 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 links:

C5orf58 (HGNC:37272): (chromosome 5 open reading frame 58)

C5orf58 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005723983).

BP6

Variant 5-170248735-A-G is Benign according to our data. Variant chr5-170248735-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2656066.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LCP2	NM_005565.5	MANE Select	c.1564T>C	p.Tyr522His	missense	Exon 21 of 21	NP_005556.1	Q13094
C5orf58	NR_131091.3		n.202-2913A>G		intron	N/A
C5orf58	NR_131092.3		n.118-2913A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LCP2	ENST00000046794.10	TSL:1 MANE Select	c.1564T>C	p.Tyr522His	missense	Exon 21 of 21	ENSP00000046794.5	Q13094
C5orf58	ENST00000524171.5	TSL:1	c.95-2913A>G		intron	N/A	ENSP00000490552.1	A0A1B0GVU6
LCP2	ENST00000968849.1		c.1573T>C	p.Tyr525His	missense	Exon 21 of 21	ENSP00000638908.1

Frequencies

GnomAD3 genomes

AF:

0.00264

AC:

402

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00349

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00440

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00268

AC:

658

AN:

245588

AF XY:

0.00269

show subpopulations

Gnomad AFR exome

AF:

0.000521

Gnomad AMR exome

AF:

0.000479

Gnomad ASJ exome

AF:

0.00282

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00363

Gnomad NFE exome

AF:

0.00426

Gnomad OTH exome

AF:

0.00352

GnomAD4 exome

AF:

0.00334

AC:

4877

AN:

1458358

Hom.:

Cov.:

AF XY:

0.00332

AC XY:

2410

AN XY:

725412

show subpopulations

African (AFR)

AF:

0.000813

AC:

AN:

33230

American (AMR)

AF:

0.000525

AC:

AN:

43814

Ashkenazi Jewish (ASJ)

AF:

0.00254

AC:

AN:

26032

East Asian (EAS)

AF:

0.00

AC:

AN:

39646

South Asian (SAS)

AF:

0.000773

AC:

AN:

85432

European-Finnish (FIN)

AF:

0.00306

AC:

163

AN:

53346

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00393

AC:

4364

AN:

1110836

Other (OTH)

AF:

0.00256

AC:

154

AN:

60264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

229

457

686

914

1143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

312

468

624

780

<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:

0.00265

AC:

403

AN:

152278

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

186

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.000505

AC:

AN:

41558

American (AMR)

AF:

0.000588

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00124

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00349

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00440

AC:

299

AN:

68016

Other (OTH)

AF:

0.00190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00337

Hom.:

Bravo

AF:

0.00239

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000253

AC:

ESP6500EA

AF:

0.00507

AC:

ExAC

AF:

0.00299

AC:

361

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00349

EpiControl

AF:

0.00416

ClinVar

ClinVar submissions

Significance:Likely 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

0.19

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

Eigen

Benign

-0.079

Eigen_PC

Benign

0.044

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.82

M_CAP

Benign

0.0076

MetaRNN

Benign

0.0057

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.90

PhyloP100

2.1

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.92

REVEL

Benign

0.11

Sift

Benign

0.26

Sift4G

Benign

0.18

Polyphen

0.90

Vest4

0.22

MVP

0.47

MPC

0.69

ClinPred

0.023

GERP RS

3.1

Varity_R

0.031

gMVP

0.33

Mutation Taster

=92/8

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