Variant X-66599693-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021783.5(EDA2R):c.685C>T(p.Pro229Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000897 in 111,506 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Consequence

EDA2R
NM_021783.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.428

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 links:

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ACMG classification

Classification made for transcript

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=0.08546585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDA2R	NM_021783.5 linkuse as main transcript	c.685C>T	p.Pro229Ser	missense_variant	6/7	ENST00000374719.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EDA2R	ENST00000374719.8 linkuse as main transcript	c.685C>T	p.Pro229Ser	missense_variant	6/7	1	NM_021783.5	P1	Q9HAV5-1
EDA2R	ENST00000253392.5 linkuse as main transcript	c.748C>T	p.Pro250Ser	missense_variant	6/6	1			Q9HAV5-2
EDA2R	ENST00000396050.5 linkuse as main transcript	c.748C>T	p.Pro250Ser	missense_variant	6/7	5			Q9HAV5-2
EDA2R	ENST00000451436.6 linkuse as main transcript	c.685C>T	p.Pro229Ser	missense_variant	6/7	5		P1	Q9HAV5-1

Frequencies

GnomAD3 genomes

AF:

0.00000897

AC:

AN:

111506

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33694

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000283

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000897

AC:

AN:

111506

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33694

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000283

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2024

The c.748C>T (p.P250S) alteration is located in exon 6 (coding exon 6) of the EDA2R gene. This alteration results from a C to T substitution at nucleotide position 748, causing the proline (P) at amino acid position 250 to be replaced by a serine (S). 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

0.094

BayesDel_addAF

Benign

-0.054

BayesDel_noAF

Benign

-0.32

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.11

T;.;T;.

FATHMM_MKL

Benign

0.34

M_CAP

Uncertain

0.099

MetaRNN

Benign

0.085

T;T;T;T

MetaSVM

Uncertain

-0.16

MutationAssessor

Benign

1.6

L;.;L;.

MutationTaster

Benign

0.54

D;D;D;D;D;D

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.4

N;.;.;N

REVEL

Benign

0.13

Sift

Pathogenic

0.0

D;.;.;D

Sift4G

Benign

0.28

T;T;T;T

Polyphen

0.19

B;B;B;B

Vest4

0.074

MutPred

0.19

Gain of sheet (P = 0.0266);.;Gain of sheet (P = 0.0266);.;

MVP

0.79

ClinPred

0.45

GERP RS

2.7

Varity_R

0.23

gMVP

0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over