Variant 1-103617585-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_000699.4(AMY2A):c.145C>G(p.Pro49Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00055 in 1,600,576 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 6 hom., cov: 31)

Exomes 𝑓: 0.00057 ( 76 hom. )

Consequence

AMY2A
NM_000699.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.55

Variant links:

Genes affected

AMY2A (HGNC:477): (amylase alpha 2A) This gene encodes a member of the alpha-amylase family of proteins. Amylases are secreted proteins that hydrolyze 1,4-alpha-glucoside bonds in oligosaccharides and polysaccharides, catalyzing the first step in digestion of dietary starch and glycogen. This gene and several family members are present in a gene cluster on chromosome 1. This gene encodes an amylase isoenzyme produced by the pancreas. [provided by RefSeq, Jan 2015]

AMY2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.873

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMY2A	NM_000699.4 linkuse as main transcript	c.145C>G	p.Pro49Ala	missense_variant	1/10	ENST00000414303.7	NP_000690.1
AMY2A	XM_047418085.1 linkuse as main transcript	c.145C>G	p.Pro49Ala	missense_variant	2/11		XP_047274041.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMY2A	ENST00000414303.7 linkuse as main transcript	c.145C>G	p.Pro49Ala	missense_variant	1/10	1	NM_000699.4	ENSP00000397582	P1	P04746-1
AMY2A	ENST00000423678.2 linkuse as main transcript	c.145C>G	p.Pro49Ala	missense_variant	1/4	3		ENSP00000390832

Frequencies

GnomAD3 genomes

AF:

0.000366

AC:

AN:

150232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000971

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:

0.000294

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000685

Gnomad OTH

AF:

0.000972

GnomAD3 exomes

AF:

0.000332

AC:

AN:

249912

Hom.:

AF XY:

0.000348

AC XY:

AN XY:

135078

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000327

Gnomad NFE exome

AF:

0.000595

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.000570

AC:

826

AN:

1450344

Hom.:

Cov.:

AF XY:

0.000587

AC XY:

424

AN XY:

721768

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000417

Gnomad4 NFE exome

AF:

0.000696

Gnomad4 OTH exome

AF:

0.000268

GnomAD4 genome

AF:

0.000366

AC:

AN:

150232

Hom.:

Cov.:

AF XY:

0.000341

AC XY:

AN XY:

73262

show subpopulations

Gnomad4 AFR

AF:

0.0000971

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000294

Gnomad4 NFE

AF:

0.000685

Gnomad4 OTH

AF:

0.000972

Alfa

AF:

0.000540

Hom.:

Bravo

AF:

0.000272

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000584

AC:

ExAC

AF:

0.000355

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2021

The c.145C>G (p.P49A) alteration is located in exon 1 (coding exon 1) of the AMY2A gene. This alteration results from a C to G substitution at nucleotide position 145, causing the proline (P) at amino acid position 49 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Uncertain

0.11

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

D;D

Eigen

Uncertain

0.29

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

D;.

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.87

D;D

MetaSVM

Uncertain

0.24

MutationAssessor

Pathogenic

3.2

M;M

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-6.8

.;D

REVEL

Pathogenic

0.87

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.62

MVP

0.96

MPC

0.56

ClinPred

0.44

GERP RS

3.2

Varity_R

0.88

gMVP

0.55

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over