rs201971844

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_178428.4(LCE2A):​c.223C>A​(p.Arg75Ser) 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. 14/20 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. R75C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

LCE2A
NM_178428.4 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.109
Variant links:
Genes affected
LCE2A (HGNC:29469): (late cornified envelope 2A) Predicted to be involved in keratinization. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06778246).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LCE2ANM_178428.4 linkc.223C>A p.Arg75Ser missense_variant Exon 2 of 2 ENST00000368779.2 NP_848515.1 Q5TA79

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LCE2AENST00000368779.2 linkc.223C>A p.Arg75Ser missense_variant Exon 2 of 2 1 NM_178428.4 ENSP00000357768.1 Q5TA79

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
5.0
DANN
Benign
0.55
DEOGEN2
Benign
0.0046
T
Eigen
Benign
-0.79
Eigen_PC
Benign
-0.89
FATHMM_MKL
Benign
0.026
N
LIST_S2
Benign
0.27
T
M_CAP
Benign
0.0036
T
MetaRNN
Benign
0.068
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.6
L
PROVEAN
Benign
-0.63
N
REVEL
Benign
0.034
Sift
Benign
0.29
T
Sift4G
Benign
0.92
T
Polyphen
0.0020
B
Vest4
0.098
MutPred
0.17
Loss of methylation at R75 (P = 0.0377);
MVP
0.33
MPC
0.0039
ClinPred
0.055
T
GERP RS
-0.37
Varity_R
0.078
gMVP
0.038

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201971844; hg19: chr1-152671600; API