1-152664389-A-T

Variant names:

• chr1-152664389-A-T
• NM_178430.4:c.284A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178430.4(LCE2D):​c.284A>T​(p.Glu95Val) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LCE2D NM_178430.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0980

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07415137).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCE2D	NM_178430.4	c.284A>T	p.Glu95Val	missense_variant	Exon 2 of 2	ENST00000368784.2	NP_848517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCE2D	ENST00000368784.2	c.284A>T	p.Glu95Val	missense_variant	Exon 2 of 2	1	NM_178430.4	ENSP00000357773.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 19, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.284A>T (p.E95V) alteration is located in exon 2 (coding exon 1) of the LCE2D gene. This alteration results from a A to T substitution at nucleotide position 284, causing the glutamic acid (E) at amino acid position 95 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.63
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0090	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.6	L
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.14
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.20	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.076		Loss of glycosylation at S94 (P = 0.0874);
MVP		0.088
MPC		0.0040
ClinPred		0.11	T
GERP RS		-5.1
Varity_R		0.29
gMVP		0.091

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-152636865;