Genetic Variant AMY2B:p.Leu31Leu (chr1-103571693-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001387437.1(AMY2B):c.91C>T(p.Leu31Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00691 in 1,611,906 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0071 ( 56 hom. )

Consequence

AMY2B
NM_001387437.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.380

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 1-103571693-C-T is Benign according to our data. Variant chr1-103571693-C-T is described in ClinVar as [Benign]. Clinvar id is 771690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.38 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMY2B	NM_001387437.1 link	c.91C>T	p.Leu31Leu	synonymous_variant	Exon 1 of 10	ENST00000684275.1	NP_001374366.1
AMY2B	NM_001386109.1 link	c.91C>T	p.Leu31Leu	synonymous_variant	Exon 3 of 12		NP_001373038.1
AMY2B	NM_020978.4 link	c.91C>T	p.Leu31Leu	synonymous_variant	Exon 3 of 12		NP_066188.1	P19961-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMY2B	ENST00000684275.1 link	c.91C>T	p.Leu31Leu	synonymous_variant	Exon 1 of 10		NM_001387437.1	ENSP00000507176.1		P19961-1

Frequencies

GnomAD3 genomes

AF:

0.00537

AC:

817

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00948

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00464

AC:

1161

AN:

250358

Hom.:

AF XY:

0.00484

AC XY:

656

AN XY:

135412

show subpopulations

Gnomad AFR exome

AF:

0.00181

Gnomad AMR exome

AF:

0.00258

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000883

Gnomad FIN exome

AF:

0.00227

Gnomad NFE exome

AF:

0.00816

Gnomad OTH exome

AF:

0.00393

GnomAD4 exome

AF:

0.00707

AC:

10323

AN:

1459648

Hom.:

Cov.:

AF XY:

0.00692

AC XY:

5028

AN XY:

726124

show subpopulations

Gnomad4 AFR exome

AF:

0.00135

Gnomad4 AMR exome

AF:

0.00268

Gnomad4 ASJ exome

AF:

0.00172

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000940

Gnomad4 FIN exome

AF:

0.00234

Gnomad4 NFE exome

AF:

0.00862

Gnomad4 OTH exome

AF:

0.00525

GnomAD4 genome

AF:

0.00537

AC:

817

AN:

152258

Hom.:

Cov.:

AF XY:

0.00484

AC XY:

360

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00264

Gnomad4 NFE

AF:

0.00948

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00379

Hom.:

Bravo

AF:

0.00502

EpiCase

AF:

0.00758

EpiControl

AF:

0.00735

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 20, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

8.6

DANN

Benign

0.79

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