rs114727970

Positions:

• chr1-109628244-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_001368809.2(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 NM_001368809.2 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: -2.00

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 -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: {Uncertain_significance=1, Benign=2, 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	UniProt
AMPD2	NM_001368809.2	c.1242C>T	p.Tyr414=	synonymous_variant	11/19	ENST00000528667.7

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00304 AC: 462 AN: 152202 Hom.: 0 Cov.: 32

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.: 1 AF XY: 0.00296 AC XY: 402 AN XY: 135704

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.: 23 Cov.: 34 AF XY: 0.00497 AC XY: 3617 AN XY: 727062

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.: 0 Cov.: 32 AF XY: 0.00261 AC XY: 194 AN XY: 74464

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.: 2

Bravo AF: 0.00311

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00485

EpiControl AF: 0.00373

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:3

Revision: criteria provided, conflicting classifications

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

Invitae

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

Other links and lift over

dbSNP: rs114727970; hg19: chr1-110170866; COSMIC: COSV56647473; COSMIC: COSV56647473;