rs41280332

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001368809.2(AMPD2):c.1407+3A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00391 in 1,612,168 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 9 hom. )

Consequence

AMPD2
NM_001368809.2 splice_region, intron

Scores

Splicing: ADA: 0.0004856

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:4

Conservation

PhyloP100: -0.304

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:

ENSG00000228703 (HGNC:):

ENSG00000228703 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 1-109628498-A-G is Benign according to our data. Variant chr1-109628498-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 434144.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=3}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00296 (451/152148) while in subpopulation NFE AF= 0.0048 (326/67976). AF 95% confidence interval is 0.00437. There are 2 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 GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMPD2	NM_001368809.2 link	c.1407+3A>G		splice_region_variant, intron_variant	Intron 12 of 18	ENST00000528667.7	NP_001355738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMPD2	ENST00000528667.7 link	c.1407+3A>G		splice_region_variant, intron_variant	Intron 12 of 18	1	NM_001368809.2	ENSP00000436541.2

Frequencies

GnomAD3 genomes

AF:

0.00296

AC:

450

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000773

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00125

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00480

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00267

AC:

666

AN:

249168

Hom.:

AF XY:

0.00271

AC XY:

366

AN XY:

134960

show subpopulations

Gnomad AFR exome

AF:

0.000250

Gnomad AMR exome

AF:

0.00179

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000980

Gnomad FIN exome

AF:

0.00400

Gnomad NFE exome

AF:

0.00410

Gnomad OTH exome

AF:

0.00377

GnomAD4 exome

AF:

0.00401

AC:

5853

AN:

1460020

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

2819

AN XY:

726404

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00104

Gnomad4 FIN exome

AF:

0.00512

Gnomad4 NFE exome

AF:

0.00470

Gnomad4 OTH exome

AF:

0.00300

GnomAD4 genome

AF:

0.00296

AC:

451

AN:

152148

Hom.:

Cov.:

AF XY:

0.00261

AC XY:

194

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.000771

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.00358

Gnomad4 NFE

AF:

0.00480

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00365

Hom.:

Bravo

AF:

0.00272

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00365

EpiControl

AF:

0.00344

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Jul 30, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

AMPD2: BP4, BS2 -

Jun 15, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Uncertain:1

Mar 28, 2017

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

AMPD2-related disorder

Benign:1

Apr 16, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hereditary spastic paraplegia 63;C4014354:Pontocerebellar hypoplasia type 9

Benign:1

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

6.8

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00049

dbscSNV1_RF

Benign

0.024

SpliceAI score (max)

0.050

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