Genetic Variant LCE2B:p.Pro29Ala (chr1-152686928-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014357.5(LCE2B):c.85C>G(p.Pro29Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P29L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

LCE2B
NM_014357.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0220

Publications

0 publications found

Variant links:

Genes affected

LCE2B (HGNC:16610): (late cornified envelope 2B) This gene is one of the at least 20 genes expressed during epidermal differentiation and located on chromosomal band 1q21. This gene is involved in epidermal differentiation, and it is expressed at high levels in normal and psoriatic skin, but not in cultured keratinocytes or in any other tested cell types or tissues. [provided by RefSeq, Jul 2008]

LCE2B links:

ENSG00000304363 (HGNC:):

ENSG00000304363 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04880154).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014357.5. 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
	LCE2B	NM_014357.5	MANE Select	c.85C>G	p.Pro29Ala	missense	Exon 2 of 2	NP_055172.1	O14633

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LCE2B	ENST00000368780.4	TSL:1 MANE Select	c.85C>G	p.Pro29Ala	missense	Exon 2 of 2	ENSP00000357769.3	O14633
ENSG00000304363	ENST00000802896.1		n.81-8411G>C		intron	N/A
ENSG00000304363	ENST00000802897.1		n.69-20202G>C		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251482

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1112008

Other (OTH)

AF:

0.0000166

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

5.6

(source)

DANN

Benign

0.27

DEOGEN2

Benign

0.080

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.46

M_CAP

Benign

0.0010

MetaRNN

Benign

0.049

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.6

PhyloP100

-0.022

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.047

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.016

Polyphen

0.0

Vest4

0.19

MutPred

0.21

Loss of glycosylation at P29 (P = 0.0047)

MVP

0.088

MPC

0.0029

ClinPred

0.092

GERP RS

0.44

Varity_R

0.068

gMVP

0.020

Mutation Taster

=98/2

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over