1-109620296-T-C

Variant names:

• chr1-109620296-T-C
• rs28362580
• NM_001368809.2:c.-263+18T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001368809.2(AMPD2):​c.-263+18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0843 in 1,612,938 control chromosomes in the GnomAD database, including 9,248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1101 hom., cov: 32)
  • Exomes 𝑓: 0.083 (8147 hom.)
• Consequence: AMPD2 NM_001368809.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.150
• Publications: 11 publications found

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]

AMPD2 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 9

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• hereditary spastic paraplegia 63

  Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-109620296-T-C is Benign according to our data. Variant chr1-109620296-T-C is described in ClinVar as Benign. ClinVar VariationId is 1255291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001368809.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMPD2	NM_001368809.2	MANE Select	c.-263+18T>C		intron	N/A	NP_001355738.1	Q01433-1
	AMPD2	NM_139156.4		c.10+18T>C		intron	N/A	NP_631895.1	Q01433-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMPD2	ENST00000528667.7	TSL:1 MANE Select	c.-263+18T>C		intron	N/A	ENSP00000436541.2	Q01433-1
	AMPD2	ENST00000342115.8	TSL:1	c.10+18T>C		intron	N/A	ENSP00000345498.4	Q01433-2
	AMPD2	ENST00000531734.6	TSL:4	c.10+18T>C		intron	N/A	ENSP00000433739.2	Q01433-2

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15340 AN: 151756 Hom.: 1103 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0574

Gnomad AMR AF: 0.0719

Gnomad ASJ AF: 0.0708

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.0587

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0580

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.110 AC: 27577 AN: 250810 AF XY: 0.115

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.0605

Gnomad ASJ exome AF: 0.0801

Gnomad EAS exome AF: 0.312

Gnomad FIN exome AF: 0.0542

Gnomad NFE exome AF: 0.0575

Gnomad OTH exome AF: 0.0908

GnomAD4 exome AF: 0.0825 AC: 120567 AN: 1461064 Hom.: 8147 Cov.: 31 AF XY: 0.0873 AC XY: 63472 AN XY: 726786

African (AFR) AF: 0.163 AC: 5464 AN: 33452

American (AMR) AF: 0.0623 AC: 2786 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.0791 AC: 2064 AN: 26100

East Asian (EAS) AF: 0.283 AC: 11229 AN: 39634

South Asian (SAS) AF: 0.265 AC: 22868 AN: 86230

European-Finnish (FIN) AF: 0.0561 AC: 2997 AN: 53384

Middle Eastern (MID) AF: 0.104 AC: 597 AN: 5766

European-Non Finnish (NFE) AF: 0.0597 AC: 66323 AN: 1111464

Other (OTH) AF: 0.103 AC: 6239 AN: 60348

GnomAD4 genome AF: 0.101 AC: 15353 AN: 151874 Hom.: 1101 Cov.: 32 AF XY: 0.106 AC XY: 7846 AN XY: 74214

African (AFR) AF: 0.150 AC: 6200 AN: 41424

American (AMR) AF: 0.0719 AC: 1098 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0708 AC: 245 AN: 3462

East Asian (EAS) AF: 0.312 AC: 1601 AN: 5126

South Asian (SAS) AF: 0.281 AC: 1344 AN: 4786

European-Finnish (FIN) AF: 0.0587 AC: 620 AN: 10570

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0580 AC: 3940 AN: 67930

Other (OTH) AF: 0.107 AC: 225 AN: 2108

Alfa AF: 0.0761 Hom.: 176

Bravo AF: 0.100

Asia WGS AF: 0.263 AC: 914 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hereditary spastic paraplegia 63 (1)
-	-	1	Pontocerebellar hypoplasia type 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.3
DANN	Benign	0.71
PhyloP100		0.15
PromoterAI		-0.0025	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28362580; hg19: chr1-110162918; COSMIC: COSV56648167; COSMIC: COSV56648167;