Variant 1-109621101-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001368809.2(AMPD2):c.-75G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,210 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

AMPD2
NM_001368809.2 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81

Variant links:

Genes affected

AMPD2 (HGNC:469): (adenosine monophosphate deaminase 2) The protein encoded by this gene is important in purine metabolism by converting AMP to IMP. The encoded protein, which acts as a homotetramer, is one of three AMP deaminases found in mammals. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

AMPD2 links:

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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	Effect	#exon/exons	MANE	Protein	UniProt
AMPD2	NM_001368809.2 link	c.-75G>T	5_prime_UTR_variant	2/19	ENST00000528667.7	NP_001355738.1
AMPD2	NM_001308170.1 link	c.-7G>T	5_prime_UTR_variant	1/17		NP_001295099.1	Q01433-4
AMPD2	NM_139156.4 link	c.10+823G>T	intron_variant			NP_631895.1	Q01433-2
AMPD2	NM_004037.9 link	c.-75G>T	upstream_gene_variant			NP_004028.4	Q01433

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMPD2	ENST00000528667 link	c.-75G>T		5_prime_UTR_variant	2/19	1	NM_001368809.2	ENSP00000436541.2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.0000131

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000482

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

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 63;C4014354:Pontocerebellar hypoplasia type 9

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 24, 2018

This variant has not been reported in the literature in individuals with AMPD2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with tryptophan at codon 30 of the AMPD2 protein (p.Gly30Trp). The glycine residue is weakly conserved and there is a large physicochemical difference between glycine and tryptophan. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.20

T;T

Eigen

Benign

0.18

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.55

.;T

M_CAP

Pathogenic

0.55

MetaRNN

Uncertain

0.47

T;T

MetaSVM

Uncertain

-0.17

MutationAssessor

Benign

0.34

N;N

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.32

N;N

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.99

D;D

Vest4

0.36

MutPred

0.47

Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);

MVP

0.90

MPC

0.79

ClinPred

0.80

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.12

gMVP

0.18

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