Variant 1-103620605-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000414303.7(AMY2A):c.799C>T(p.Arg267Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 21)

Exomes 𝑓: 0.000015 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

AMY2A
ENST00000414303.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.74

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.919

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMY2A	NM_000699.4 linkuse as main transcript	c.799C>T	p.Arg267Trp	missense_variant	5/10	ENST00000414303.7	NP_000690.1	P04746-1Q53F26
AMY2A	XM_047418085.1 linkuse as main transcript	c.799C>T	p.Arg267Trp	missense_variant	6/11		XP_047274041.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMY2A	ENST00000414303.7 linkuse as main transcript	c.799C>T	p.Arg267Trp	missense_variant	5/10	1	NM_000699.4	ENSP00000397582.2		P04746-1
AMY2A	ENST00000423678.2 linkuse as main transcript	c.568C>T	p.Arg190Trp	missense_variant	4/4	3		ENSP00000390832.2		H7BZQ8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000151

AC:

AN:

198424

Hom.:

AF XY:

0.00000928

AC XY:

AN XY:

107720

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000322

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000153

AC:

AN:

1434872

Hom.:

Cov.:

AF XY:

0.0000154

AC XY:

AN XY:

714514

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.0000458

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000165

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000249

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

Apr 08, 2024

The c.799C>T (p.R267W) alteration is located in exon 5 (coding exon 5) of the AMY2A gene. This alteration results from a C to T substitution at nucleotide position 799, causing the arginine (R) at amino acid position 267 to be replaced by a tryptophan (W). 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

0.32

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.85

D;D

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.83

LIST_S2

Pathogenic

0.99

D;.

M_CAP

Uncertain

0.27

MetaRNN

Pathogenic

0.92

D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.8

H;H

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-5.8

.;D

REVEL

Pathogenic

0.88

Sift

Uncertain

0.011

.;D

Sift4G

Benign

0.17

T;T

Polyphen

1.0

D;D

Vest4

0.86

MutPred

0.67

Loss of methylation at R267 (P = 0.0124);Loss of methylation at R267 (P = 0.0124);

MVP

0.98

MPC

3.3

ClinPred

0.99

GERP RS

2.0

Varity_R

0.84

gMVP

0.65

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