rs34030799

Variant names:

• chr1-109628106-G-A
• rs34030799
• NM_001368809.2:c.1104G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-109628106-G-A
• chr1-109628106-G-C
• chr1-109628106-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001368809.2(AMPD2):​c.1104G>A​(p.Ser368Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0227 in 1,613,870 control chromosomes in the GnomAD database, including 602 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (41 hom., cov: 32)
  • Exomes 𝑓: 0.023 (561 hom.)
• Consequence: AMPD2 NM_001368809.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.70
• Publications: 5 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.047).
• BP6: Variant 1-109628106-G-A is Benign according to our data. Variant chr1-109628106-G-A is described in ClinVar as Benign. ClinVar VariationId is 474994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.7 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0524 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.1104G>A	p.Ser368Ser	synonymous	Exon 11 of 19	NP_001355738.1	Q01433-1
	AMPD2	NM_004037.9		c.1104G>A	p.Ser368Ser	synonymous	Exon 10 of 18	NP_004028.4
	AMPD2	NM_001308170.1		c.1041G>A	p.Ser347Ser	synonymous	Exon 9 of 17	NP_001295099.1	Q01433-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMPD2	ENST00000528667.7	TSL:1 MANE Select	c.1104G>A	p.Ser368Ser	synonymous	Exon 11 of 19	ENSP00000436541.2	Q01433-1
	AMPD2	ENST00000342115.8	TSL:1	c.1023G>A	p.Ser341Ser	synonymous	Exon 10 of 18	ENSP00000345498.4	Q01433-2
	AMPD2	ENST00000526301.6	TSL:1	n.1167G>A		non_coding_transcript_exon	Exon 10 of 18

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2472 AN: 152204 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.00603

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00942

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0588

Gnomad FIN AF: 0.00735

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0233

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.0199 AC: 5002 AN: 251042 AF XY: 0.0222

Gnomad AFR exome AF: 0.00646

Gnomad AMR exome AF: 0.00665

Gnomad ASJ exome AF: 0.0254

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.00828

Gnomad NFE exome AF: 0.0226

Gnomad OTH exome AF: 0.0165

GnomAD4 exome AF: 0.0234 AC: 34146 AN: 1461548 Hom.: 561 Cov.: 34 AF XY: 0.0241 AC XY: 17544 AN XY: 727082

African (AFR) AF: 0.00496 AC: 166 AN: 33478

American (AMR) AF: 0.00689 AC: 308 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 655 AN: 26126

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39698

South Asian (SAS) AF: 0.0514 AC: 4431 AN: 86238

European-Finnish (FIN) AF: 0.00836 AC: 445 AN: 53250

Middle Eastern (MID) AF: 0.0237 AC: 136 AN: 5748

European-Non Finnish (NFE) AF: 0.0240 AC: 26647 AN: 1111906

Other (OTH) AF: 0.0224 AC: 1353 AN: 60388

GnomAD4 genome AF: 0.0162 AC: 2469 AN: 152322 Hom.: 41 Cov.: 32 AF XY: 0.0160 AC XY: 1194 AN XY: 74480

African (AFR) AF: 0.00601 AC: 250 AN: 41566

American (AMR) AF: 0.00941 AC: 144 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 83 AN: 3472

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.0580 AC: 280 AN: 4828

European-Finnish (FIN) AF: 0.00735 AC: 78 AN: 10614

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0233 AC: 1583 AN: 68034

Other (OTH) AF: 0.0132 AC: 28 AN: 2114

Alfa AF: 0.0179 Hom.: 21

Bravo AF: 0.0148

Asia WGS AF: 0.0210 AC: 73 AN: 3478

EpiCase AF: 0.0243

EpiControl AF: 0.0233

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	Hereditary spastic paraplegia 63;C4014354:Pontocerebellar hypoplasia type 9 (1)
-	-	1	Pontocerebellar hypoplasia type 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	2.1
DANN	Benign	0.84
PhyloP100		-3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
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: rs34030799; hg19: chr1-110170728;