1-103573840-C-A
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001387437.1(AMY2B):c.646C>A(p.His216Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
AMY2B
NM_001387437.1 missense
NM_001387437.1 missense
Scores
15
2
1
Clinical Significance
Conservation
PhyloP100: 6.05
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.992
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AMY2B | NM_001387437.1 | c.646C>A | p.His216Asn | missense_variant | 4/10 | ENST00000684275.1 | |
AMY2B | NM_001386109.1 | c.646C>A | p.His216Asn | missense_variant | 6/12 | ||
AMY2B | NM_020978.4 | c.646C>A | p.His216Asn | missense_variant | 6/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AMY2B | ENST00000684275.1 | c.646C>A | p.His216Asn | missense_variant | 4/10 | NM_001387437.1 | P1 | ||
AMY2B | ENST00000361355.8 | c.646C>A | p.His216Asn | missense_variant | 6/12 | 1 | P1 | ||
AMY2B | ENST00000491397.1 | n.3915C>A | non_coding_transcript_exon_variant | 4/9 | 5 | ||||
AMY2B | ENST00000477657.5 | c.646C>A | p.His216Asn | missense_variant, NMD_transcript_variant | 5/10 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461570Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 727098
GnomAD4 exome
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1
AN:
1461570
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35
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1
AN XY:
727098
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
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 | Aug 30, 2022 | The c.646C>A (p.H216N) alteration is located in exon 6 (coding exon 4) of the AMY2B gene. This alteration results from a C to A substitution at nucleotide position 646, causing the histidine (H) at amino acid position 216 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;H
MutationTaster
Benign
D
PrimateAI
Pathogenic
T
PROVEAN
Pathogenic
D;.
REVEL
Pathogenic
Sift
Pathogenic
D;.
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Gain of helix (P = 0.062);Gain of helix (P = 0.062);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.