Variant 1-103573100-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001387437.1(AMY2B):c.353C>G(p.Ser118Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000117 in 1,613,712 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

AMY2B
NM_001387437.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.49

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12579092).

BP6

Variant 1-103573100-C-G is Benign according to our data. Variant chr1-103573100-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3117329.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AMY2B	NM_001387437.1 linkuse as main transcript	c.353C>G	p.Ser118Cys	missense_variant	3/10	ENST00000684275.1
AMY2B	NM_001386109.1 linkuse as main transcript	c.353C>G	p.Ser118Cys	missense_variant	5/12
AMY2B	NM_020978.4 linkuse as main transcript	c.353C>G	p.Ser118Cys	missense_variant	5/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMY2B	ENST00000684275.1 linkuse as main transcript	c.353C>G	p.Ser118Cys	missense_variant	3/10		NM_001387437.1	P1	P19961-1
AMY2B	ENST00000361355.8 linkuse as main transcript	c.353C>G	p.Ser118Cys	missense_variant	5/12	1		P1	P19961-1
AMY2B	ENST00000491397.1 linkuse as main transcript	n.3622C>G		non_coding_transcript_exon_variant	3/9	5
AMY2B	ENST00000477657.5 linkuse as main transcript	c.353C>G	p.Ser118Cys	missense_variant, NMD_transcript_variant	4/10	2			P19961-2

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000220

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000518

AC:

AN:

251078

Hom.:

AF XY:

0.0000737

AC XY:

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000105

AC:

154

AN:

1461432

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000116

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000230

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.000189

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.028

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.53

DEOGEN2

Uncertain

0.57

D;D

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.14

M_CAP

Benign

0.036

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.36

MutationAssessor

Benign

-1.3

N;N

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.59

PROVEAN

Benign

2.4

N;.

REVEL

Uncertain

0.36

Sift

Benign

1.0

T;.

Sift4G

Benign

0.47

T;T

Polyphen

0.0

B;B

Vest4

0.37

MVP

0.42

MPC

0.12

ClinPred

0.010

GERP RS

-1.1

Varity_R

0.042

gMVP

0.76

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