Variant chr14-69209669-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001193360.2(EXD2):c.199A>G(p.Arg67Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,268 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

EXD2
NM_001193360.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17

Variant links:

Genes affected

EXD2 (HGNC:20217): (exonuclease 3'-5' domain containing 2) Enables 3'-5' exonuclease activity; metal ion binding activity; and protein homodimerization activity. Involved in nucleic acid metabolic process. Located in intermediate filament cytoskeleton; mitochondrial outer membrane; and site of DNA damage. [provided by Alliance of Genome Resources, Apr 2022]

EXD2 links:

EXD2 (HGNC:):

EXD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0535672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXD2	NM_001193360.2 linkuse as main transcript	c.199A>G	p.Arg67Gly	missense_variant	3/10	ENST00000685843.1	NP_001180289.1	Q9NVH0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXD2	ENST00000685843.1 linkuse as main transcript	c.199A>G	p.Arg67Gly	missense_variant	3/10		NM_001193360.2	ENSP00000510642.1		Q9NVH0-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Dec 15, 2023

The c.199A>G (p.R67G) alteration is located in exon 3 (coding exon 1) of the EXD2 gene. This alteration results from a A to G substitution at nucleotide position 199, causing the arginine (R) at amino acid position 67 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

0.066

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.47

DEOGEN2

Benign

0.0046

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.31

.;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.054

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.6

L;L

PrimateAI

Benign

0.29

PROVEAN

Benign

0.060

N;N

REVEL

Benign

0.11

Sift

Benign

0.081

T;T

Sift4G

Benign

0.29

T;T

Vest4

0.086

MutPred

0.39

Loss of solvent accessibility (P = 0.0329);Loss of solvent accessibility (P = 0.0329);

MVP

0.38

MPC

0.19

ClinPred

0.041

GERP RS

1.6

Varity_R

0.043

gMVP

0.36

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