1-109628182-G-T

Variant names:

• chr1-109628182-G-T
• rs374249741
• NM_001368809.2:c.1180G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001368809.2(AMPD2):​c.1180G>T​(p.Val394Leu) variant causes a missense 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V394M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AMPD2 NM_001368809.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• Publications: 1 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: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics
• hereditary spastic paraplegia 63

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

ENSG00000228703 (HGNC:40074):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21849445).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMPD2	NM_001368809.2	c.1180G>T	p.Val394Leu	missense_variant	Exon 11 of 19	ENST00000528667.7	NP_001355738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMPD2	ENST00000528667.7	c.1180G>T	p.Val394Leu	missense_variant	Exon 11 of 19	1	NM_001368809.2	ENSP00000436541.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	23
DANN	Benign	0.94
DEOGEN2	Uncertain	0.48	.;T;T;.;.;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D;.;D;D;D;D
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.22	T;T;T;T;T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	0.040	.;N;N;.;.;.
PhyloP100		2.0
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.52	N;N;N;N;N;N
REVEL	Benign	0.28
Sift	Benign	0.65	T;T;T;T;T;T
Sift4G	Benign	0.66	T;T;T;T;T;T
Polyphen		0.0090	B;B;B;B;.;B
Vest4		0.44
MutPred		0.44		.;Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);.;.;.;
MVP		0.78
MPC		0.88
ClinPred		0.25	T
GERP RS		4.1
Varity_R		0.095
gMVP		0.89
Mutation Taster		=78/22	polymorphism

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: rs374249741; hg19: chr1-110170804;