Genetic Variant NM_001387437.1:c.74G>A (chr1-103571676-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001387437.1(AMY2B):c.74G>A(p.Arg25Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,611,864 control chromosomes in the GnomAD database, including 4 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00088 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

AMY2B
NM_001387437.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.24

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024542063).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387437.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMY2B	NM_001387437.1	MANE Select	c.74G>A	p.Arg25Gln	missense	Exon 1 of 10	NP_001374366.1	P19961-1
AMY2B	NM_001386109.1		c.74G>A	p.Arg25Gln	missense	Exon 3 of 12	NP_001373038.1	P19961-1
AMY2B	NM_020978.4		c.74G>A	p.Arg25Gln	missense	Exon 3 of 12	NP_066188.1	P19961-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMY2B	ENST00000684275.1	MANE Select	c.74G>A	p.Arg25Gln	missense	Exon 1 of 10	ENSP00000507176.1	P19961-1
AMY2B	ENST00000361355.8	TSL:1	c.74G>A	p.Arg25Gln	missense	Exon 3 of 12	ENSP00000354610.4	P19961-1
AMY2B	ENST00000435302.5	TSL:3	c.74G>A	p.Arg25Gln	missense	Exon 3 of 4	ENSP00000391423.1	C9J2Z5

Frequencies

GnomAD3 genomes

AF:

0.000881

AC:

134

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

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:

0.000755

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00165

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000992

AC:

248

AN:

249914

AF XY:

0.000976

show subpopulations

Gnomad AFR exome

AF:

0.000568

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000742

Gnomad NFE exome

AF:

0.00190

Gnomad OTH exome

AF:

0.000494

GnomAD4 exome

AF:

0.00117

AC:

1713

AN:

1459644

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

828

AN XY:

726124

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

33406

American (AMR)

AF:

0.000112

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86162

European-Finnish (FIN)

AF:

0.000861

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.00145

AC:

1610

AN:

1111794

Other (OTH)

AF:

0.000664

AC:

AN:

60200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

113

227

340

454

567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000880

AC:

134

AN:

152220

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41526

American (AMR)

AF:

0.00

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000755

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00165

AC:

112

AN:

68022

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00106

Hom.:

Bravo

AF:

0.000748

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00126

AC:

153

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.55

Eigen

Benign

-0.036

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.56

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.020

MetaRNN

Benign

0.025

MetaSVM

Benign

-0.93

MutationAssessor

Pathogenic

3.3

PhyloP100

2.2

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.17

Sift

Uncertain

0.015

Sift4G

Uncertain

0.025

Polyphen

0.89

Vest4

0.24

MVP

0.72

MPC

0.34

ClinPred

0.086

GERP RS

1.9

PromoterAI

-0.0053

Neutral

(source)

Varity_R

0.31

gMVP

0.71

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over