Variant rs114727970 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The ENST00000528667.7(AMPD2):c.1242C>T(p.Tyr414=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00501 in 1,613,894 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 23 hom. )

Consequence

AMPD2
ENST00000528667.7 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: -2.00

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 1-109628244-C-T is Benign according to our data. Variant chr1-109628244-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 210136.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Uncertain_significance=1, Likely_benign=1}.

BP7

Synonymous conserved (PhyloP=-2 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00303 (462/152320) while in subpopulation NFE AF= 0.00553 (376/68046). AF 95% confidence interval is 0.00506. There are 0 homozygotes in gnomad4. There are 194 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMPD2	NM_001368809.2 linkuse as main transcript	c.1242C>T	p.Tyr414=	synonymous_variant	11/19	ENST00000528667.7	NP_001355738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMPD2	ENST00000528667.7 linkuse as main transcript	c.1242C>T	p.Tyr414=	synonymous_variant	11/19	1	NM_001368809.2	ENSP00000436541	P1

Frequencies

GnomAD3 genomes

AF:

0.00304

AC:

462

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00553

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00294

AC:

738

AN:

251110

Hom.:

AF XY:

0.00296

AC XY:

402

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.000862

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.000974

Gnomad NFE exome

AF:

0.00560

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00522

AC:

7629

AN:

1461574

Hom.:

Cov.:

AF XY:

0.00497

AC XY:

3617

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.000836

Gnomad4 AMR exome

AF:

0.00123

Gnomad4 ASJ exome

AF:

0.000497

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.00124

Gnomad4 NFE exome

AF:

0.00644

Gnomad4 OTH exome

AF:

0.00457

GnomAD4 genome

AF:

0.00303

AC:

462

AN:

152320

Hom.:

Cov.:

AF XY:

0.00261

AC XY:

194

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00553

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00400

Hom.:

Bravo

AF:

0.00311

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00485

EpiControl

AF:

0.00373

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	AMPD2: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 16, 2020	- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 28, 2015

- -

Hereditary spastic paraplegia 63;C4014354:Pontocerebellar hypoplasia type 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

3.5

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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