ENST00000531734.6:c.-129-444G>C

Variant names:

• chr1-109619696-G-C
• rs77539911
• ENST00000872463.1:c.-175C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000531734.6(AMPD2):​c.-129-444G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00461 in 164,766 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0050 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: AMPD2 ENST00000531734.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.682
• Publications: 0 publications found

Genes affected

GNAT2 (HGNC:4394): (G protein subunit alpha transducin 2) Transducin is a 3-subunit guanine nucleotide-binding protein (G protein) which stimulates the coupling of rhodopsin and cGMP-phoshodiesterase during visual impulses. The transducin alpha subunits in rods and cones are encoded by separate genes. This gene encodes the alpha subunit in cones. [provided by RefSeq, Jul 2008]

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 1-109619696-G-C is Benign according to our data. Variant chr1-109619696-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1223444.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00496 (756/152368) while in subpopulation AFR AF = 0.0177 (738/41586). AF 95% confidence interval is 0.0167. There are 5 homozygotes in GnomAd4. There are 332 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000531734.6. 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.-845G>C		upstream_gene	N/A	NP_001355738.1	Q01433-1
	GNAT2	NM_001377295.2	MANE Select	c.-267C>G		upstream_gene	N/A	NP_001364224.1	P19087
	AMPD2	NM_139156.4		c.-573G>C		upstream_gene	N/A	NP_631895.1	Q01433-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAT2	ENST00000872463.1		c.-175C>G		5_prime_UTR	Exon 1 of 9	ENSP00000542522.1
	AMPD2	ENST00000531734.6	TSL:4	c.-129-444G>C		intron	N/A	ENSP00000433739.2	Q01433-2
	GNAT2	ENST00000622865.1	TSL:3	c.-54+192C>G		intron	N/A	ENSP00000482596.1	A0A087WZE5

Frequencies

GnomAD3 genomes AF: 0.00495 AC: 753 AN: 152250 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0177

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.000242 AC: 3 AN: 12398 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 7006

African (AFR) AF: 0.00 AC: 0 AN: 42

American (AMR) AF: 0.00176 AC: 3 AN: 1704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 166

East Asian (EAS) AF: 0.00 AC: 0 AN: 78

South Asian (SAS) AF: 0.00 AC: 0 AN: 3434

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 22

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 5942

Other (OTH) AF: 0.00 AC: 0 AN: 518

GnomAD4 genome AF: 0.00496 AC: 756 AN: 152368 Hom.: 5 Cov.: 33 AF XY: 0.00446 AC XY: 332 AN XY: 74514

African (AFR) AF: 0.0177 AC: 738 AN: 41586

American (AMR) AF: 0.000914 AC: 14 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00374 Hom.: 0

Bravo AF: 0.00511

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		-0.68
PromoterAI		-0.22	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs77539911; hg19: chr1-110162318;