1-109620296-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001368809.2(AMPD2):c.-263+18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0843 in 1,612,938 control chromosomes in the GnomAD database, including 9,248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1101 hom., cov: 32)
  • Exomes 𝑓: 0.083 (8147 hom.)
• Consequence: AMPD2 NM_001368809.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.150

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-109620296-T-C is Benign according to our data. Variant chr1-109620296-T-C is described in ClinVar as [Benign]. Clinvar id is 1255291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMPD2	NM_001368809.2	c.-263+18T>C		intron_variant		ENST00000528667.7
AMPD2	NM_139156.4	c.10+18T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMPD2	ENST00000528667.7	c.-263+18T>C		intron_variant		1	NM_001368809.2	P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15340 AN: 151756 Hom.: 1103 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0574

Gnomad AMR AF: 0.0719

Gnomad ASJ AF: 0.0708

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.0587

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0580

Gnomad OTH AF: 0.105

GnomAD3 exomes AF: 0.110 AC: 27577 AN: 250810 Hom.: 2576 AF XY: 0.115 AC XY: 15634 AN XY: 135530

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.0605

Gnomad ASJ exome AF: 0.0801

Gnomad EAS exome AF: 0.312

Gnomad SAS exome AF: 0.270

Gnomad FIN exome AF: 0.0542

Gnomad NFE exome AF: 0.0575

Gnomad OTH exome AF: 0.0908

GnomAD4 exome AF: 0.0825 AC: 120567 AN: 1461064 Hom.: 8147 Cov.: 31 AF XY: 0.0873 AC XY: 63472 AN XY: 726786

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.0623

Gnomad4 ASJ exome AF: 0.0791

Gnomad4 EAS exome AF: 0.283

Gnomad4 SAS exome AF: 0.265

Gnomad4 FIN exome AF: 0.0561

Gnomad4 NFE exome AF: 0.0597

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.101 AC: 15353 AN: 151874 Hom.: 1101 Cov.: 32 AF XY: 0.106 AC XY: 7846 AN XY: 74214

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0719

Gnomad4 ASJ AF: 0.0708

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.0587

Gnomad4 NFE AF: 0.0580

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0761 Hom.: 176

Bravo AF: 0.100

Asia WGS AF: 0.263 AC: 914 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hereditary spastic paraplegia 63 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

Pontocerebellar hypoplasia type 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	9.3
Dann	Benign	0.71

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

Other links and lift over

dbSNP: rs28362580; hg19: chr1-110162918; COSMIC: COSV56648167; COSMIC: COSV56648167;