1-109619926-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001368809.2(AMPD2):c.-615C>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 0.119 in 364,084 control chromosomes in the GnomAD database, including 4,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (2092 hom., cov: 33)
  • Exomes 𝑓: 0.11 (2170 hom.)
• Consequence: AMPD2 NM_001368809.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.546

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]

GNAT2 (HGNC:4394): (G protein subunit alpha transducin 2) Transducin is a 3-subunit guanine nucleotide-binding protein (G protein) which stimulates the coupling of rhodopsin and cGMP-phoshodiesterase during visual impulses. The transducin alpha subunits in rods and cones are encoded by separate genes. This gene encodes the alpha subunit in cones. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 1-109619926-C-T is Benign according to our data. Variant chr1-109619926-C-T is described in ClinVar as [Benign]. Clinvar id is 1256631.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMPD2	NM_001368809.2	c.-615C>T		5_prime_UTR_variant	1/19	ENST00000528667.7
AMPD2	NM_139156.4	c.-343C>T		5_prime_UTR_variant	1/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMPD2	ENST00000528667.7	c.-615C>T		5_prime_UTR_variant	1/19	1	NM_001368809.2	P1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20363 AN: 152126 Hom.: 2093 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0830

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.0567

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0579

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.107 AC: 22760 AN: 211838 Hom.: 2170 Cov.: 0 AF XY: 0.124 AC XY: 14337 AN XY: 115402

Gnomad4 AFR exome AF: 0.251

Gnomad4 AMR exome AF: 0.0700

Gnomad4 ASJ exome AF: 0.0741

Gnomad4 EAS exome AF: 0.261

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.0513

Gnomad4 NFE exome AF: 0.0551

Gnomad4 OTH exome AF: 0.0968

GnomAD4 genome AF: 0.134 AC: 20389 AN: 152246 Hom.: 2092 Cov.: 33 AF XY: 0.136 AC XY: 10139 AN XY: 74428

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.0829

Gnomad4 ASJ AF: 0.0726

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.0567

Gnomad4 NFE AF: 0.0579

Gnomad4 OTH AF: 0.128

Alfa AF: 0.0985 Hom.: 170

Bravo AF: 0.138

Asia WGS AF: 0.269 AC: 935 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.74
Cadd	Benign	9.3
Dann	Benign	0.88
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: rs55646629; hg19: chr1-110162548; COSMIC: COSV104559407; COSMIC: COSV104559407;