1-109621133-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001368809.2(AMPD2):c.-43G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000083 in 1,445,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: AMPD2 NM_001368809.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.44

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18823883).
• BP6: Variant 1-109621133-G-T is Benign according to our data. Variant chr1-109621133-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1546575.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMPD2	NM_001368809.2	c.-43G>T		5_prime_UTR_variant	2/19	ENST00000528667.7
AMPD2	NM_001308170.1	c.26G>T	p.Gly9Val	missense_variant	1/17
AMPD2	NM_139156.4	c.10+855G>T		intron_variant
AMPD2	NM_004037.9			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMPD2	ENST00000528667.7	c.-43G>T		5_prime_UTR_variant	2/19	1	NM_001368809.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000419 AC: 9 AN: 214696 Hom.: 0 AF XY: 0.0000339 AC XY: 4 AN XY: 117916

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000215

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000365

GnomAD4 exome AF: 0.00000830 AC: 12 AN: 1445996 Hom.: 0 Cov.: 35 AF XY: 0.00000696 AC XY: 5 AN XY: 718398

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000253

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.06e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary spastic paraplegia 63;C4014354:Pontocerebellar hypoplasia type 9 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Mar 20, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Uncertain	0.070
Cadd	Benign	17
Dann	Uncertain	0.98
Eigen	Benign	-0.086
Eigen_PC	Benign	-0.089
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.48	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.89	D;D;D;D
PROVEAN	Benign	0.69	N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.23	T
Polyphen		0.94	P
Vest4		0.40
MutPred		0.17		Loss of loop (P = 0.0203);
MVP		0.61
ClinPred		0.12	T
GERP RS		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs768664971; hg19: chr1-110163755;