Genetic Variant EDA2R:p.Leu160Phe (chrX-66602672-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021783.5(EDA2R):c.478C>T(p.Leu160Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000919 in 1,088,436 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.2e-7 ( 0 hom. 1 hem. )

Consequence

EDA2R
NM_021783.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0970

Publications

0 publications found

Variant links:

Genes affected

EDA2R (HGNC:17756): (ectodysplasin A2 receptor) The protein encoded by this gene is a type III transmembrane protein of the TNFR (tumor necrosis factor receptor) superfamily, and contains cysteine-rich repeats and a single transmembrane domain. This protein binds to the EDA-A2 isoform of ectodysplasin, which plays an important role in maintenance of hair and teeth. Alternatively spliced transcript variants encodes distinct protein isoforms. [provided by RefSeq, Apr 2016]

EDA2R Gene-Disease associations (from GenCC):

X-linked hypohidrotic ectodermal dysplasia
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

EDA2R links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2136155).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021783.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EDA2R	NM_021783.5	MANE Select	c.478C>T	p.Leu160Phe	missense	Exon 5 of 7	NP_068555.2	Q9HAV5-1
EDA2R	NM_001242310.1		c.478C>T	p.Leu160Phe	missense	Exon 4 of 7	NP_001229239.1	Q9HAV5
EDA2R	NM_001324206.2		c.478C>T	p.Leu160Phe	missense	Exon 5 of 7	NP_001311135.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EDA2R	ENST00000374719.8	TSL:1 MANE Select	c.478C>T	p.Leu160Phe	missense	Exon 5 of 7	ENSP00000363851.3	Q9HAV5-1
EDA2R	ENST00000253392.5	TSL:1	c.478C>T	p.Leu160Phe	missense	Exon 4 of 6	ENSP00000253392.5	Q9HAV5-2
EDA2R	ENST00000396050.5	TSL:5	c.478C>T	p.Leu160Phe	missense	Exon 4 of 7	ENSP00000379365.2	Q9HAV5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.19e-7

AC:

AN:

1088436

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

355906

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26193

American (AMR)

AF:

0.00

AC:

AN:

34175

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19148

East Asian (EAS)

AF:

0.00

AC:

AN:

29710

South Asian (SAS)

AF:

0.00

AC:

AN:

52488

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39899

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4108

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

836987

Other (OTH)

AF:

0.00

AC:

AN:

45728

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.11

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.11

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.74

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.63

PhyloP100

0.097

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.2

REVEL

Benign

0.20

Sift

Benign

0.27

Sift4G

Benign

0.45

Polyphen

0.0050

Vest4

0.15

MutPred

0.24

Loss of sheet (P = 0.1158)

MVP

0.81

ClinPred

0.093

GERP RS

0.26

Varity_R

0.19

gMVP

0.23

Mutation Taster

=88/12

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over