1-152664146-C-A

Variant names:

• chr1-152664146-C-A
• NM_178430.4:c.41C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_178430.4(LCE2D):​c.41C>A​(p.Pro14His) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LCE2D NM_178430.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.19
• Publications: 0 publications found

Genes affected

LCE2D (HGNC:16518): (late cornified envelope 2D) Predicted to be involved in keratinization. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000304363 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35651925).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178430.4. 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
	LCE2D	NM_178430.4	MANE Select	c.41C>A	p.Pro14His	missense	Exon 2 of 2	NP_848517.1	Q5TA82

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCE2D	ENST00000368784.2	TSL:1 MANE Select	c.41C>A	p.Pro14His	missense	Exon 2 of 2	ENSP00000357773.1	Q5TA82
	ENSG00000304363	ENST00000802896.1		n.420+2415G>T		intron	N/A
	ENSG00000304363	ENST00000802897.1		n.234+2415G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Benign	0.84
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	-0.0010
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		2.2
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.053
Sift	Benign	0.059	T
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.20		Loss of glycosylation at P14 (P = 0.0017)
MVP		0.64
MPC		0.0040
ClinPred		0.77	D
GERP RS		3.0
Varity_R		0.28
gMVP		0.053
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chr1-152636622; COSMIC: COSV64229122;