chr1-109621131-C-G

Variant names:

• chr1-109621131-C-G
• rs1030974786
• NM_001368809.2:c.-45C>G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001308170.1(AMPD2):​c.24C>G​(p.Ala8Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,446,226 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A8A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: AMPD2 NM_001308170.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03537622).
• BP7: Synonymous conserved (PhyloP=-0.047 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMPD2	NM_001368809.2	c.-45C>G		5_prime_UTR_variant	Exon 2 of 19	ENST00000528667.7	NP_001355738.1
AMPD2	NM_001308170.1	c.24C>G	p.Ala8Ala	synonymous_variant	Exon 1 of 17		NP_001295099.1
AMPD2	NM_139156.4	c.10+853C>G		intron_variant	Intron 1 of 17		NP_631895.1
AMPD2	NM_004037.9	c.-45C>G		upstream_gene_variant			NP_004028.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMPD2	ENST00000528667	c.-45C>G		5_prime_UTR_variant	Exon 2 of 19	1	NM_001368809.2	ENSP00000436541.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000277 AC: 4 AN: 1446226 Hom.: 0 Cov.: 34 AF XY: 0.00000278 AC XY: 2 AN XY: 718544

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000362

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Benign	0.81
DEOGEN2	Benign	0.22	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.40	.;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.035	T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.010	N;N
REVEL	Benign	0.25
Sift	Benign	0.86	T;T
Sift4G	Benign	0.67	T;T
Polyphen		0.0	B;B
Vest4		0.072
MutPred		0.17		Loss of methylation at R40 (P = 0.0666);Loss of methylation at R40 (P = 0.0666);
MVP		0.54
MPC		0.87
ClinPred		0.041	T
GERP RS		-1.2
Varity_R		0.057
gMVP		0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs1030974786; hg19: chr1-110163753;