1-152664369-C-A

Variant names:

• chr1-152664369-C-A
• NM_178430.4:c.264C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178430.4(LCE2D):​c.264C>A​(p.Ser88Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,224 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LCE2D NM_178430.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.649

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 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=0.06180036).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCE2D	NM_178430.4	c.264C>A	p.Ser88Arg	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.264C>A	p.Ser88Arg	missense_variant	Exon 2 of 2	1	NM_178430.4	ENSP00000357773.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456224 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 724438

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.264C>A (p.S88R) alteration is located in exon 2 (coding exon 1) of the LCE2D gene. This alteration results from a C to A substitution at nucleotide position 264, causing the serine (S) at amino acid position 88 to be replaced by an arginine (R). 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	0.29
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.0
DANN	Benign	0.46
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.9	L
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.052
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.60	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.085		Loss of phosphorylation at S88 (P = 0.0239);
MVP		0.055
MPC		0.0041
ClinPred		0.11	T
GERP RS		-1.1
Varity_R		0.30
gMVP		0.066

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-152636845;