Variant X-66605082-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021783.5(EDA2R):c.232A>C(p.Thr78Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000457 in 1,094,626 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000046 ( 0 hom. 0 hem. )

Consequence

EDA2R
NM_021783.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.13

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDA2R	NM_021783.5 link	c.232A>C	p.Thr78Pro	missense_variant	3/7	ENST00000374719.8	NP_068555.2	Q9HAV5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EDA2R	ENST00000374719.8 link	c.232A>C	p.Thr78Pro	missense_variant	3/7	1	NM_021783.5	ENSP00000363851.3	Q9HAV5-1
EDA2R	ENST00000253392.5 link	c.232A>C	p.Thr78Pro	missense_variant	2/6	1		ENSP00000253392.5	Q9HAV5-2
EDA2R	ENST00000396050.5 link	c.232A>C	p.Thr78Pro	missense_variant	2/7	5		ENSP00000379365.2	Q9HAV5-2
EDA2R	ENST00000451436.6 link	c.232A>C	p.Thr78Pro	missense_variant	3/7	5		ENSP00000415242.3	Q9HAV5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000457

AC:

AN:

1094626

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

360452

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000119

Gnomad4 OTH exome

AF:

0.0000870

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Aug 21, 2023

The c.232A>C (p.T78P) alteration is located in exon 2 (coding exon 2) of the EDA2R gene. This alteration results from a A to C substitution at nucleotide position 232, causing the threonine (T) at amino acid position 78 to be replaced by a proline (P). 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

Uncertain

0.43

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.89

D;.;D;.

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.81

.;T;T;.

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.58

D;D;D;D

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.5

M;M;M;M

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-5.0

D;D;.;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.0060

D;D;.;D

Sift4G

Uncertain

0.0040

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.45

MutPred

0.76

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);

MVP

0.52

ClinPred

0.99

GERP RS

3.9

Varity_R

0.96

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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