rs201971844

Variant names:

• chr1-152699124-C-A
• rs201971844
• NM_178428.4:c.223C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-152699124-C-A
• chr1-152699124-C-G
• chr1-152699124-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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. 15/21 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109
• Publications: 2 publications found

Genes affected

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

ENSG00000304363 (HGNC:):

ACMG classification

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=0.06778246).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178428.4. 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
	LCE2A	NM_178428.4	MANE Select	c.223C>A	p.Arg75Ser	missense	Exon 2 of 2	NP_848515.1	Q5TA79

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCE2A	ENST00000368779.2	TSL:1 MANE Select	c.223C>A	p.Arg75Ser	missense	Exon 2 of 2	ENSP00000357768.1	Q5TA79
	ENSG00000304363	ENST00000802896.1		n.81-20607G>T		intron	N/A
	ENSG00000304363	ENST00000802897.1		n.69-32398G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.11
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
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

dbSNP: rs201971844; hg19: chr1-152671600;