chr1-109621109-T-C

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 10P and 2B. PVS1PM2BP6_Moderate

The NM_001308170.1(AMPD2):c.2T>C(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000567 in 1,603,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

AMPD2
NM_001308170.1 start_lost

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.224

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_pathogenic. The variant received 8 ACMG points.

PVS1

Start lost variant, next in-frame start position is after 12 pathogenic variants. Next in-frame start position is after 180 codons. Genomic position: 109626795. Lost 0.223 part of the original CDS.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 1-109621109-T-C is Benign according to our data. Variant chr1-109621109-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1135001.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308170.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMPD2	NM_001368809.2	MANE Select	c.-67T>C		5_prime_UTR	Exon 2 of 19	NP_001355738.1	Q01433-1
AMPD2	NM_001308170.1		c.2T>C	p.Met1?	start_lost	Exon 1 of 17	NP_001295099.1	Q01433-4
AMPD2	NM_139156.4		c.10+831T>C		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.-67T>C	5_prime_UTR	Exon 2 of 19	ENSP00000436541.2	Q01433-1
AMPD2	ENST00000342115.8	TSL:1	c.10+831T>C	intron	N/A	ENSP00000345498.4	Q01433-2
AMPD2	ENST00000369840.7	TSL:5	c.-67T>C	5_prime_UTR	Exon 1 of 18	ENSP00000358855.3	H0Y360

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000222

AC:

AN:

225184

AF XY:

0.0000323

show subpopulations

Gnomad AFR exome

AF:

0.0000784

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000408

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000599

AC:

AN:

1451626

Hom.:

Cov.:

AF XY:

0.0000665

AC XY:

AN XY:

721592

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33096

American (AMR)

AF:

0.00

AC:

AN:

44188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25946

East Asian (EAS)

AF:

0.00

AC:

AN:

39160

South Asian (SAS)

AF:

0.00

AC:

AN:

85012

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51822

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4994

European-Non Finnish (NFE)

AF:

0.0000776

AC:

AN:

1107628

Other (OTH)

AF:

0.00

AC:

AN:

59780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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

AF:

0.0000263

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000330

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

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_addAF

Benign

0.0091

BayesDel_noAF

Uncertain

0.030

CADD

Benign

(source)

DANN

Benign

0.86

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.80

MetaRNN

Pathogenic

0.93

MetaSVM

Benign

-0.52

PhyloP100

0.22

PROVEAN

Pathogenic

-5.0

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

Polyphen

0.0010

Vest4

0.85

MutPred

0.98

Gain of glycosylation at M1 (P = 0.0156)

MVP

0.74

ClinPred

0.13

GERP RS

4.0

PromoterAI

0.30

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=51/149

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over