dbSNP rs201058957: LCE2D:p.Ala99Gly (chr1-152664401-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_178430.4(LCE2D):c.296C>G(p.Ala99Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000336 in 1,606,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

LCE2D
NM_178430.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0340

Publications

0 publications found

Variant links:

Genes affected

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

LCE2D links:

ENSG00000304363 (HGNC:):

ENSG00000304363 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020536691).

BP6

Variant 1-152664401-C-G is Benign according to our data. Variant chr1-152664401-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2375833.Status of the report is criteria_provided_single_submitter, 1 stars.

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.296C>G	p.Ala99Gly	missense	Exon 2 of 2	NP_848517.1	Q5TA82

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LCE2D	ENST00000368784.2	TSL:1 MANE Select	c.296C>G	p.Ala99Gly	missense	Exon 2 of 2	ENSP00000357773.1	Q5TA82
ENSG00000304363	ENST00000802896.1		n.420+2160G>C		intron	N/A
ENSG00000304363	ENST00000802897.1		n.234+2160G>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000564

AC:

AN:

248204

AF XY:

0.0000519

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000713

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.0000316

AC:

AN:

1454714

Hom.:

Cov.:

AF XY:

0.0000345

AC XY:

AN XY:

723640

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33392

American (AMR)

AF:

0.0000675

AC:

AN:

44432

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25962

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85722

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53096

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.0000343

AC:

AN:

1106712

Other (OTH)

AF:

0.0000667

AC:

AN:

60014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152062

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41386

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000711

Hom.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000495

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.037

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.42

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.0076

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00022

LIST_S2

Benign

0.18

M_CAP

Benign

0.00089

MetaRNN

Benign

0.021

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.0

PhyloP100

0.034

PROVEAN

Benign

0.57

REVEL

Benign

0.030

Sift

Benign

0.80

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.043

MutPred

0.11

Loss of glycosylation at S94 (P = 0.1531)

MVP

0.040

MPC

0.0043

ClinPred

0.015

GERP RS

0.98

Varity_R

0.031

gMVP

0.021

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over