Variant chrX-66599773-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_021783.5(EDA2R):c.605C>T(p.Ser202Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,096,501 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 18 hemizygotes 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: not found (cov: 22)

Exomes 𝑓: 0.000035 ( 0 hom. 18 hem. )

Consequence

EDA2R
NM_021783.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.748

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05346158).

BS2

High Hemizygotes in GnomAdExome4 at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDA2R	NM_021783.5 linkuse as main transcript	c.605C>T	p.Ser202Phe	missense_variant	6/7	ENST00000374719.8	NP_068555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDA2R	ENST00000374719.8 linkuse as main transcript	c.605C>T	p.Ser202Phe	missense_variant	6/7	1	NM_021783.5	ENSP00000363851	P1	Q9HAV5-1
EDA2R	ENST00000253392.5 linkuse as main transcript	c.668C>T	p.Ser223Phe	missense_variant	6/6	1		ENSP00000253392		Q9HAV5-2
EDA2R	ENST00000396050.5 linkuse as main transcript	c.668C>T	p.Ser223Phe	missense_variant	6/7	5		ENSP00000379365		Q9HAV5-2
EDA2R	ENST00000451436.6 linkuse as main transcript	c.605C>T	p.Ser202Phe	missense_variant	6/7	5		ENSP00000415242	P1	Q9HAV5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000169

AC:

AN:

177733

Hom.:

AF XY:

0.00

AC XY:

AN XY:

62871

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000370

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000253

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000347

AC:

AN:

1096501

Hom.:

Cov.:

AF XY:

0.0000497

AC XY:

AN XY:

362039

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000570

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:

0.0000428

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ExAC

AF:

0.00000824

AC:

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

Nov 08, 2021

The c.668C>T (p.S223F) 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 668, causing the serine (S) at amino acid position 223 to be replaced by a phenylalanine (F). 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

0.085

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.48

CADD

Benign

7.7

DANN

Benign

0.14

DEOGEN2

Benign

0.15

T;.;T;.

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.58

.;T;T;.

M_CAP

Benign

0.0085

MetaRNN

Benign

0.053

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.;N;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.3

N;D;.;N

REVEL

Benign

0.055

Sift

Benign

0.82

T;D;.;T

Sift4G

Benign

0.30

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.15

MutPred

0.21

Loss of sheet (P = 0.0126);.;Loss of sheet (P = 0.0126);.;

MVP

0.68

ClinPred

0.041

GERP RS

0.070

Varity_R

0.059

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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