chrX-66604439-G-A

Position:

chrX-66604439-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_021783.5(EDA2R):c.334C>T(p.Pro112Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00387 in 1,206,820 control chromosomes in the GnomAD database, including 11 homozygotes. There are 1,482 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., 66 hem., cov: 22)

Exomes 𝑓: 0.0040 ( 10 hom. 1416 hem. )

Consequence

EDA2R
NM_021783.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 5.18

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007465422).

BP6

Variant X-66604439-G-A is Benign according to our data. Variant chrX-66604439-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 718792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-66604439-G-A is described in Lovd as [Benign].

BS2

High Hemizygotes in GnomAd4 at 66 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDA2R	NM_021783.5 linkuse as main transcript	c.334C>T	p.Pro112Ser	missense_variant	4/7	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.334C>T	p.Pro112Ser	missense_variant	4/7	1	NM_021783.5	ENSP00000363851	P1	Q9HAV5-1
EDA2R	ENST00000253392.5 linkuse as main transcript	c.334C>T	p.Pro112Ser	missense_variant	3/6	1		ENSP00000253392		Q9HAV5-2
EDA2R	ENST00000396050.5 linkuse as main transcript	c.334C>T	p.Pro112Ser	missense_variant	3/7	5		ENSP00000379365		Q9HAV5-2
EDA2R	ENST00000451436.6 linkuse as main transcript	c.334C>T	p.Pro112Ser	missense_variant	4/7	5		ENSP00000415242	P1	Q9HAV5-1

Frequencies

GnomAD3 genomes

AF:

0.00233

AC:

260

AN:

111498

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

AN XY:

33678

show subpopulations

Gnomad AFR

AF:

0.000556

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00113

Gnomad ASJ

AF:

0.00493

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000384

Gnomad FIN

AF:

0.000827

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00396

Gnomad OTH

AF:

0.00135

GnomAD3 exomes

AF:

0.00230

AC:

416

AN:

180972

Hom.:

AF XY:

0.00229

AC XY:

150

AN XY:

65624

show subpopulations

Gnomad AFR exome

AF:

0.000382

Gnomad AMR exome

AF:

0.000557

Gnomad ASJ exome

AF:

0.00420

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000108

Gnomad FIN exome

AF:

0.000377

Gnomad NFE exome

AF:

0.00432

Gnomad OTH exome

AF:

0.00157

GnomAD4 exome

AF:

0.00403

AC:

4414

AN:

1095268

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

1416

AN XY:

361012

show subpopulations

Gnomad4 AFR exome

AF:

0.000380

Gnomad4 AMR exome

AF:

0.000683

Gnomad4 ASJ exome

AF:

0.00585

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000112

Gnomad4 FIN exome

AF:

0.000717

Gnomad4 NFE exome

AF:

0.00489

Gnomad4 OTH exome

AF:

0.00250

GnomAD4 genome

AF:

0.00233

AC:

260

AN:

111552

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

AN XY:

33742

show subpopulations

Gnomad4 AFR

AF:

0.000554

Gnomad4 AMR

AF:

0.00113

Gnomad4 ASJ

AF:

0.00493

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000385

Gnomad4 FIN

AF:

0.000827

Gnomad4 NFE

AF:

0.00396

Gnomad4 OTH

AF:

0.00133

Alfa

AF:

0.00360

Hom.:

Bravo

AF:

0.00241

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00485

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00372

AC:

ExAC

AF:

0.00246

AC:

299

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 14, 2018	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

D;.;D;.

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.88

.;D;D;.

M_CAP

Benign

0.067

MetaRNN

Benign

0.0075

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;L;L

MutationTaster

Benign

1.0

D;N;N;N;N;N

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-6.1

D;D;.;D

REVEL

Benign

0.18

Sift

Uncertain

0.0020

D;D;.;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.82

P;D;P;D

Vest4

0.32

MVP

0.19

ClinPred

0.13

GERP RS

3.4

Varity_R

0.63

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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