NM_001368809.2:c.-119G>C

Variant names:

• chr1-109621057-G-C
• NM_001368809.2:c.-119G>C

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.-119G>C variant causes a 5 prime UTR 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AMPD2 NM_001368809.2 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.67
• Publications: 0 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: 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=0.14378661).

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.-119G>C		5_prime_UTR	Exon 2 of 19	NP_001355738.1	Q01433-1
	AMPD2	NM_001308170.1		c.-51G>C		5_prime_UTR	Exon 1 of 17	NP_001295099.1	Q01433-4
	AMPD2	NM_139156.4		c.10+779G>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.-119G>C		5_prime_UTR	Exon 2 of 19	ENSP00000436541.2	Q01433-1
	AMPD2	ENST00000342115.8	TSL:1	c.10+779G>C		intron	N/A	ENSP00000345498.4	Q01433-2
	AMPD2	ENST00000256578.8	TSL:5	c.-119G>C		5_prime_UTR	Exon 1 of 18	ENSP00000256578.4	Q01433-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Hereditary spastic paraplegia 63;C4014354:Pontocerebellar hypoplasia type 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.015
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N
PhyloP100		1.7
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.083
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.20
MutPred		0.32		Gain of phosphorylation at C15 (P = 0.011)
MVP		0.52
MPC		0.81
ClinPred		0.24	T
GERP RS		3.9
PromoterAI		-0.31	Neutral
Varity_R		0.62
gMVP		0.41
Mutation Taster		=86/14	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

hg19: chr1-110163679;