Variant 1-103617510-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000699.4(AMY2A):c.70G>A(p.Gly24Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AMY2A
NM_000699.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.54

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMY2A	NM_000699.4 linkuse as main transcript	c.70G>A	p.Gly24Arg	missense_variant	1/10	ENST00000414303.7	NP_000690.1
AMY2A	XM_047418085.1 linkuse as main transcript	c.70G>A	p.Gly24Arg	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.70G>A	p.Gly24Arg	missense_variant	1/10	1	NM_000699.4	ENSP00000397582	P1	P04746-1
AMY2A	ENST00000423678.2 linkuse as main transcript	c.70G>A	p.Gly24Arg	missense_variant	1/4	3		ENSP00000390832

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000207

AC:

AN:

1450316

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

721758

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 10, 2024

The c.70G>A (p.G24R) alteration is located in exon 1 (coding exon 1) of the AMY2A gene. This alteration results from a G to A substitution at nucleotide position 70, causing the glycine (G) at amino acid position 24 to be replaced by an arginine (R). 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

0.23

BayesDel_addAF

Uncertain

0.082

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

T;T

Eigen

Benign

0.10

Eigen_PC

Benign

-0.026

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

D;.

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.70

D;D

MetaSVM

Uncertain

-0.10

MutationAssessor

Pathogenic

3.2

M;M

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-4.9

.;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0010

.;D

Sift4G

Uncertain

0.028

D;D

Polyphen

0.97

D;D

Vest4

0.59

MutPred

0.40

Gain of catalytic residue at G24 (P = 0.0669);Gain of catalytic residue at G24 (P = 0.0669);

MVP

0.61

MPC

0.75

ClinPred

0.99

GERP RS

3.2

Varity_R

0.82

gMVP

0.72

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