Variant 1-103573781-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001387437.1(AMY2B):c.587A>T(p.Glu196Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,720 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

AMY2B
NM_001387437.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.56

Variant links:

Genes affected

AMY2B (HGNC:478): (amylase alpha 2B) Amylases are secreted proteins that hydrolyze 1,4-alpha-glucoside bonds in oligosaccharides and polysaccharides, and thus catalyze the first step in digestion of dietary starch and glycogen. The human genome has a cluster of several amylase genes that are expressed at high levels in either salivary gland or pancreas. This gene encodes an amylase isoenzyme produced by the pancreas. [provided by RefSeq, Jun 2013]

AMY2B 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
AMY2B	NM_001387437.1 linkuse as main transcript	c.587A>T	p.Glu196Val	missense_variant	4/10	ENST00000684275.1
AMY2B	NM_001386109.1 linkuse as main transcript	c.587A>T	p.Glu196Val	missense_variant	6/12
AMY2B	NM_020978.4 linkuse as main transcript	c.587A>T	p.Glu196Val	missense_variant	6/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMY2B	ENST00000684275.1 linkuse as main transcript	c.587A>T	p.Glu196Val	missense_variant	4/10		NM_001387437.1	P1	P19961-1
AMY2B	ENST00000361355.8 linkuse as main transcript	c.587A>T	p.Glu196Val	missense_variant	6/12	1		P1	P19961-1
AMY2B	ENST00000491397.1 linkuse as main transcript	n.3856A>T		non_coding_transcript_exon_variant	4/9	5
AMY2B	ENST00000477657.5 linkuse as main transcript	c.587A>T	p.Glu196Val	missense_variant, NMD_transcript_variant	5/10	2			P19961-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461544

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Jul 14, 2022

The c.587A>T (p.E196V) alteration is located in exon 6 (coding exon 4) of the AMY2B gene. This alteration results from a A to T substitution at nucleotide position 587, causing the glutamic acid (E) at amino acid position 196 to be replaced by a valine (V). 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

0.25

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Pathogenic

0.90

D;D

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.16

M_CAP

Uncertain

0.085

MetaRNN

Uncertain

0.57

D;D

MetaSVM

Uncertain

0.52

MutationAssessor

Pathogenic

3.4

M;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Pathogenic

-4.6

D;.

REVEL

Uncertain

0.45

Sift

Uncertain

0.0020

D;.

Sift4G

Uncertain

0.057

T;T

Polyphen

0.17

B;B

Vest4

0.59

MutPred

0.62

Gain of ubiquitination at K193 (P = 0.0825);Gain of ubiquitination at K193 (P = 0.0825);

MVP

0.79

MPC

0.28

ClinPred

0.68

GERP RS

2.2

Varity_R

0.33

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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