chr1-109620373-A-G

Position:

• chr1-109620373-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001368809.2(AMPD2):​c.-263+95A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00891 in 1,564,120 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0091 (93 hom.)
• Consequence: AMPD2 NM_001368809.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0560

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=-0.88).
• BP6: Variant 1-109620373-A-G is Benign according to our data. Variant chr1-109620373-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1207664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00685 (1044/152302) while in subpopulation NFE AF= 0.011 (745/68000). AF 95% confidence interval is 0.0103. There are 4 homozygotes in gnomad4. There are 499 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMPD2	NM_001368809.2	c.-263+95A>G		intron_variant		ENST00000528667.7	NP_001355738.1
AMPD2	NM_139156.4	c.10+95A>G		intron_variant			NP_631895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMPD2	ENST00000528667.7	c.-263+95A>G		intron_variant		1	NM_001368809.2	ENSP00000436541	P1

Frequencies

GnomAD3 genomes AF: 0.00686 AC: 1044 AN: 152184 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00392

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0110

Gnomad OTH AF: 0.00334

GnomAD4 exome AF: 0.00914 AC: 12900 AN: 1411818 Hom.: 93 AF XY: 0.00882 AC XY: 6162 AN XY: 699020

Gnomad4 AFR exome AF: 0.00148

Gnomad4 AMR exome AF: 0.00205

Gnomad4 ASJ exome AF: 0.00271

Gnomad4 EAS exome AF: 0.0000257

Gnomad4 SAS exome AF: 0.00207

Gnomad4 FIN exome AF: 0.0124

Gnomad4 NFE exome AF: 0.0107

Gnomad4 OTH exome AF: 0.00638

GnomAD4 genome AF: 0.00685 AC: 1044 AN: 152302 Hom.: 4 Cov.: 32 AF XY: 0.00670 AC XY: 499 AN XY: 74470

Gnomad4 AFR AF: 0.00156

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0135

Gnomad4 NFE AF: 0.0110

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00910 Hom.: 2

Bravo AF: 0.00603

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.8
DANN	Benign	0.61

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: rs114804066; hg19: chr1-110162995;