Variant chr1-103618955-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000699.4(AMY2A):c.360C>T(p.Asn120Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 1,417,174 control chromosomes in the GnomAD database, including 257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 12 hom., cov: 27)

Exomes 𝑓: 0.020 ( 245 hom. )

Consequence

AMY2A
NM_000699.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.26

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-103618955-C-T is Benign according to our data. Variant chr1-103618955-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 774798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.26 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.017 (2266/133534) while in subpopulation NFE AF= 0.0228 (1382/60736). AF 95% confidence interval is 0.0218. There are 12 homozygotes in gnomad4. There are 1134 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMY2A	NM_000699.4 link	c.360C>T	p.Asn120Asn	synonymous_variant	3/10	ENST00000414303.7	NP_000690.1	P04746-1Q53F26
AMY2A	XM_047418085.1 link	c.360C>T	p.Asn120Asn	synonymous_variant	4/11		XP_047274041.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMY2A	ENST00000414303.7 link	c.360C>T	p.Asn120Asn	synonymous_variant	3/10	1	NM_000699.4	ENSP00000397582.2		P04746-1
AMY2A	ENST00000423678.2 link	c.360C>T	p.Asn120Asn	synonymous_variant	3/4	3		ENSP00000390832.2		H7BZQ8

Frequencies

GnomAD3 genomes

AF:

0.0170

AC:

2265

AN:

133418

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00303

Gnomad AMI

AF:

0.0337

Gnomad AMR

AF:

0.0174

Gnomad ASJ

AF:

0.0316

Gnomad EAS

AF:

0.000202

Gnomad SAS

AF:

0.00594

Gnomad FIN

AF:

0.0441

Gnomad MID

AF:

0.0500

Gnomad NFE

AF:

0.0227

Gnomad OTH

AF:

0.0211

GnomAD3 exomes

AF:

0.0183

AC:

2942

AN:

160688

Hom.:

AF XY:

0.0194

AC XY:

1662

AN XY:

85516

show subpopulations

Gnomad AFR exome

AF:

0.00287

Gnomad AMR exome

AF:

0.0130

Gnomad ASJ exome

AF:

0.0331

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00604

Gnomad FIN exome

AF:

0.0325

Gnomad NFE exome

AF:

0.0246

Gnomad OTH exome

AF:

0.0238

GnomAD4 exome

AF:

0.0204

AC:

26161

AN:

1283640

Hom.:

245

Cov.:

AF XY:

0.0201

AC XY:

12771

AN XY:

634442

show subpopulations

Gnomad4 AFR exome

AF:

0.00322

Gnomad4 AMR exome

AF:

0.0134

Gnomad4 ASJ exome

AF:

0.0300

Gnomad4 EAS exome

AF:

0.000184

Gnomad4 SAS exome

AF:

0.00525

Gnomad4 FIN exome

AF:

0.0319

Gnomad4 NFE exome

AF:

0.0221

Gnomad4 OTH exome

AF:

0.0213

GnomAD4 genome

AF:

0.0170

AC:

2266

AN:

133534

Hom.:

Cov.:

AF XY:

0.0177

AC XY:

1134

AN XY:

64206

show subpopulations

Gnomad4 AFR

AF:

0.00304

Gnomad4 AMR

AF:

0.0173

Gnomad4 ASJ

AF:

0.0316

Gnomad4 EAS

AF:

0.000203

Gnomad4 SAS

AF:

0.00594

Gnomad4 FIN

AF:

0.0441

Gnomad4 NFE

AF:

0.0228

Gnomad4 OTH

AF:

0.0214

Alfa

AF:

0.0173

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 22, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.6

DANN

Benign

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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