1-109628106-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001368809.2(AMPD2):​c.1104G>C​(p.Ser368Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S368S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AMPD2 NM_001368809.2 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.047).
• BP7: Synonymous conserved (PhyloP=-3.7 with no splicing effect.

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>C	p.Ser368Ser	synonymous	Exon 11 of 19	NP_001355738.1	Q01433-1
	AMPD2	NM_004037.9		c.1104G>C	p.Ser368Ser	synonymous	Exon 10 of 18	NP_004028.4
	AMPD2	NM_001308170.1		c.1041G>C	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>C	p.Ser368Ser	synonymous	Exon 11 of 19	ENSP00000436541.2	Q01433-1
	AMPD2	ENST00000342115.8	TSL:1	c.1023G>C	p.Ser341Ser	synonymous	Exon 10 of 18	ENSP00000345498.4	Q01433-2
	AMPD2	ENST00000526301.6	TSL:1	n.1167G>C		non_coding_transcript_exon	Exon 10 of 18

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 21

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.6
DANN	Benign	0.73
PhyloP100		-3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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;