NM_021783.5:c.823G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021783.5(EDA2R):c.823G>C(p.Gly275Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,188,190 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G275W) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.000020 ( 0 hom. 7 hem. )

Consequence

EDA2R
NM_021783.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.491

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04923317).

BP6

Variant X-66599555-C-G is Benign according to our data. Variant chrX-66599555-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3087119.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 3 XL gene

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.823G>C	p.Gly275Arg	missense	Exon 6 of 7	NP_068555.2	Q9HAV5-1
EDA2R	NM_001242310.1		c.886G>C	p.Gly296Arg	missense	Exon 6 of 7	NP_001229239.1	Q9HAV5
EDA2R	NM_001324206.2		c.829G>C	p.Gly277Arg	missense	Exon 6 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.823G>C	p.Gly275Arg	missense	Exon 6 of 7	ENSP00000363851.3	Q9HAV5-1
EDA2R	ENST00000253392.5	TSL:1	c.886G>C	p.Gly296Arg	missense	Exon 6 of 6	ENSP00000253392.5	Q9HAV5-2
EDA2R	ENST00000396050.5	TSL:5	c.886G>C	p.Gly296Arg	missense	Exon 6 of 7	ENSP00000379365.2	Q9HAV5-2

Frequencies

GnomAD3 genomes

AF:

0.0000540

AC:

AN:

111143

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000656

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000287

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000168

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000757

AC:

AN:

145361

AF XY:

0.0000230

show subpopulations

Gnomad AFR exome

AF:

0.0000954

Gnomad AMR exome

AF:

0.000169

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000892

Gnomad FIN exome

AF:

0.000376

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000204

AC:

AN:

1077047

Hom.:

Cov.:

AF XY:

0.0000200

AC XY:

AN XY:

349829

show subpopulations

African (AFR)

AF:

0.000154

AC:

AN:

26026

American (AMR)

AF:

0.000155

AC:

AN:

32335

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18984

East Asian (EAS)

AF:

0.0000344

AC:

AN:

29109

South Asian (SAS)

AF:

0.00

AC:

AN:

51370

European-Finnish (FIN)

AF:

0.000153

AC:

AN:

39272

Middle Eastern (MID)

AF:

0.000244

AC:

AN:

4104

European-Non Finnish (NFE)

AF:

0.00000241

AC:

AN:

830527

Other (OTH)

AF:

0.0000662

AC:

AN:

45320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000540

AC:

AN:

111143

Hom.:

Cov.:

AF XY:

0.0000899

AC XY:

AN XY:

33361

show subpopulations

African (AFR)

AF:

0.0000656

AC:

AN:

30509

American (AMR)

AF:

0.000287

AC:

AN:

10471

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2645

East Asian (EAS)

AF:

0.00

AC:

AN:

3515

South Asian (SAS)

AF:

0.00

AC:

AN:

2633

European-Finnish (FIN)

AF:

0.000168

AC:

AN:

5948

Middle Eastern (MID)

AF:

0.00

AC:

AN:

234

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53017

Other (OTH)

AF:

0.00

AC:

AN:

1487

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000529

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.073

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.11

(source)

DANN

Benign

0.35

DEOGEN2

Benign

0.066

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.60

M_CAP

Benign

0.037

MetaRNN

Benign

0.049

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.14

PhyloP100

-0.49

PrimateAI

Benign

0.24

PROVEAN

Benign

0.36

REVEL

Benign

0.21

Sift

Benign

0.47

Sift4G

Benign

0.91

Polyphen

0.0

Vest4

0.064

MutPred

0.15

Gain of methylation at G275 (P = 0.0463)

MVP

0.73

ClinPred

0.0052

GERP RS

0.83

Varity_R

0.036

gMVP

0.14

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over