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GeneBe

X-66599718-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_021783.5(EDA2R):c.660C>T(p.Asp220=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000472 in 1,207,892 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 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 0.000072 ( 0 hom., 2 hem., cov: 22)
Exomes 𝑓: 0.000045 ( 0 hom. 14 hem. )

Consequence

EDA2R
NM_021783.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.50
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant X-66599718-G-A is Benign according to our data. Variant chrX-66599718-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 724005.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.5 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Hemizygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EDA2RNM_021783.5 linkuse as main transcriptc.660C>T p.Asp220= synonymous_variant 6/7 ENST00000374719.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EDA2RENST00000374719.8 linkuse as main transcriptc.660C>T p.Asp220= synonymous_variant 6/71 NM_021783.5 P1Q9HAV5-1
EDA2RENST00000253392.5 linkuse as main transcriptc.723C>T p.Asp241= synonymous_variant 6/61 Q9HAV5-2
EDA2RENST00000396050.5 linkuse as main transcriptc.723C>T p.Asp241= synonymous_variant 6/75 Q9HAV5-2
EDA2RENST00000451436.6 linkuse as main transcriptc.660C>T p.Asp220= synonymous_variant 6/75 P1Q9HAV5-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000717
AC:
8
AN:
111499
Hom.:
0
Cov.:
22
AF XY:
0.0000594
AC XY:
2
AN XY:
33679
show subpopulations
Gnomad AFR
AF:
0.0000326
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000379
Gnomad FIN
AF:
0.000165
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000943
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000731
AC:
13
AN:
177850
Hom.:
0
AF XY:
0.0000318
AC XY:
2
AN XY:
62950
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000222
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000738
Gnomad SAS exome
AF:
0.0000557
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000379
Gnomad OTH exome
AF:
0.000452
GnomAD4 exome
AF:
0.0000447
AC:
49
AN:
1096393
Hom.:
0
Cov.:
32
AF XY:
0.0000387
AC XY:
14
AN XY:
361987
show subpopulations
Gnomad4 AFR exome
AF:
0.0000379
Gnomad4 AMR exome
AF:
0.000228
Gnomad4 ASJ exome
AF:
0.0000518
Gnomad4 EAS exome
AF:
0.0000332
Gnomad4 SAS exome
AF:
0.0000747
Gnomad4 FIN exome
AF:
0.0000247
Gnomad4 NFE exome
AF:
0.0000309
Gnomad4 OTH exome
AF:
0.000109
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000717
AC:
8
AN:
111499
Hom.:
0
Cov.:
22
AF XY:
0.0000594
AC XY:
2
AN XY:
33679
show subpopulations
Gnomad4 AFR
AF:
0.0000326
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000379
Gnomad4 FIN
AF:
0.000165
Gnomad4 NFE
AF:
0.0000943
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000145
Hom.:
2
Bravo
AF:
0.0000453

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 24, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
Cadd
Benign
0.11
Dann
Benign
0.61

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

LitVar

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

Other links and lift over

dbSNP: rs749216567; hg19: chrX-65819560; COSMIC: COSV53633218; API