dbSNP rs759948714: AMPD2:c.-112G>A (chr1-109621064-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001368809.2(AMPD2):c.-112G>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00000549 in 1,457,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

AMPD2
NM_001368809.2 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.02

Publications

0 publications found

Variant links:

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

AMPD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 1-109621064-G-A is Benign according to our data. Variant chr1-109621064-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 706538.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AMPD2	NM_001368809.2	MANE Select	c.-112G>A	5_prime_UTR	Exon 2 of 19	NP_001355738.1	Q01433-1
AMPD2	NM_001308170.1		c.-44G>A	5_prime_UTR	Exon 1 of 17	NP_001295099.1	Q01433-4
AMPD2	NM_139156.4		c.10+786G>A	intron	N/A	NP_631895.1	Q01433-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AMPD2	ENST00000528667.7	TSL:1 MANE Select	c.-112G>A	5_prime_UTR	Exon 2 of 19	ENSP00000436541.2	Q01433-1
AMPD2	ENST00000342115.8	TSL:1	c.10+786G>A	intron	N/A	ENSP00000345498.4	Q01433-2
AMPD2	ENST00000256578.8	TSL:5	c.-112G>A	5_prime_UTR	Exon 1 of 18	ENSP00000256578.4	Q01433-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000165

AC:

AN:

242434

AF XY:

0.00000754

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1457136

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724610

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33400

American (AMR)

AF:

0.000158

AC:

AN:

44372

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26002

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.00

AC:

AN:

85864

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52426

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4838

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1110444

Other (OTH)

AF:

0.00

AC:

AN:

60140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary spastic paraplegia 63;C4014354:Pontocerebellar hypoplasia type 9 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

4.0

PromoterAI

-0.64

Under-expression

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over