1-109620454-A-G

Position:

• chr1-109620454-A-G

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+176A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 805,526 control chromosomes in the GnomAD database, including 115,199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (22643 hom., cov: 31)
  • Exomes 𝑓: 0.53 (92556 hom.)
• Consequence: AMPD2 NM_001368809.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.210

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=-0.87).
• BP6: Variant 1-109620454-A-G is Benign according to our data. Variant chr1-109620454-A-G is described in ClinVar as [Benign]. Clinvar id is 1271710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMPD2	NM_001368809.2	c.-263+176A>G		intron_variant		ENST00000528667.7	NP_001355738.1
AMPD2	NM_139156.4	c.10+176A>G		intron_variant			NP_631895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMPD2	ENST00000528667.7	c.-263+176A>G		intron_variant		1	NM_001368809.2	ENSP00000436541	P1

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81067 AN: 151776 Hom.: 22625 Cov.: 31

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.573

GnomAD4 exome AF: 0.528 AC: 345363 AN: 653632 Hom.: 92556 AF XY: 0.529 AC XY: 160980 AN XY: 304244

Gnomad4 AFR exome AF: 0.402

Gnomad4 AMR exome AF: 0.675

Gnomad4 ASJ exome AF: 0.577

Gnomad4 EAS exome AF: 0.945

Gnomad4 SAS exome AF: 0.680

Gnomad4 FIN exome AF: 0.608

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.560

GnomAD4 genome AF: 0.534 AC: 81125 AN: 151894 Hom.: 22643 Cov.: 31 AF XY: 0.543 AC XY: 40312 AN XY: 74234

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.572

Gnomad4 EAS AF: 0.958

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.577

Alfa AF: 0.515 Hom.: 4509

Bravo AF: 0.534

Asia WGS AF: 0.768 AC: 2669 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.8
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6669802; hg19: chr1-110163076;