Variant 13-46777574-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001984.2(ESD):c.650A>G(p.Asp217Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000154 in 1,610,444 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

ESD
NM_001984.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.16

Variant links:

Genes affected

ESD (HGNC:3465): (esterase D) This gene encodes a serine hydrolase that belongs to the esterase D family. The encoded enzyme is active toward numerous substrates including O-acetylated sialic acids, and it may be involved in the recycling of sialic acids. This gene is used as a genetic marker for retinoblastoma and Wilson's disease. [provided by RefSeq, Feb 2009]

ESD links:

Genome browser will be placed here

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
ESD	NM_001984.2 linkuse as main transcript	c.650A>G	p.Asp217Gly	missense_variant	9/10	ENST00000378720.8
ESD	XM_005266278.4 linkuse as main transcript	c.650A>G	p.Asp217Gly	missense_variant	9/10
ESD	XM_011534954.2 linkuse as main transcript	c.650A>G	p.Asp217Gly	missense_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ESD	ENST00000378720.8 linkuse as main transcript	c.650A>G	p.Asp217Gly	missense_variant	9/10	1	NM_001984.2	P1
ESD	ENST00000471867.3 linkuse as main transcript	c.650A>G	p.Asp217Gly	missense_variant	9/9	2
ESD	ENST00000378697.5 linkuse as main transcript	c.563A>G	p.Asp188Gly	missense_variant	10/11	5
ESD	ENST00000412582.5 linkuse as main transcript	c.494A>G	p.Asp165Gly	missense_variant	5/6	3

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

151864

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.000962

GnomAD3 exomes

AF:

0.0000920

AC:

AN:

250110

Hom.:

AF XY:

0.0000887

AC XY:

AN XY:

135224

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

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:

0.000195

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000147

AC:

215

AN:

1458580

Hom.:

Cov.:

AF XY:

0.000163

AC XY:

118

AN XY:

725452

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000449

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:

0.000185

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000217

AC:

AN:

151864

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

AN XY:

74186

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.000962

Alfa

AF:

0.000346

Hom.:

Bravo

AF:

0.000185

ExAC

AF:

0.0000824

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

Jun 11, 2021

The c.650A>G (p.D217G) alteration is located in exon 9 (coding exon 7) of the ESD gene. This alteration results from a A to G substitution at nucleotide position 650, causing the aspartic acid (D) at amino acid position 217 to be replaced by a glycine (G). 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

0.25

BayesDel_addAF

Benign

-0.0077

BayesDel_noAF

Uncertain

0.040

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.19

T;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.67

D;D

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.25

Sift

Benign

0.25

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.0050

B;.

Vest4

0.96

MVP

0.55

MPC

0.13

ClinPred

0.12

GERP RS

6.2

Varity_R

0.79

gMVP

0.78

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.

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