chr1-103573735-C-G

Variant names:

• chr1-103573735-C-G
• NM_001387437.1:c.541C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001387437.1(AMY2B):​c.541C>G​(p.Leu181Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: AMY2B NM_001387437.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.96

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMY2B	NM_001387437.1	c.541C>G	p.Leu181Val	missense_variant	Exon 4 of 10	ENST00000684275.1	NP_001374366.1
AMY2B	NM_001386109.1	c.541C>G	p.Leu181Val	missense_variant	Exon 6 of 12		NP_001373038.1
AMY2B	NM_020978.4	c.541C>G	p.Leu181Val	missense_variant	Exon 6 of 12		NP_066188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMY2B	ENST00000684275.1	c.541C>G	p.Leu181Val	missense_variant	Exon 4 of 10		NM_001387437.1	ENSP00000507176.1
AMY2B	ENST00000361355.8	c.541C>G	p.Leu181Val	missense_variant	Exon 6 of 12	1		ENSP00000354610.4
AMY2B	ENST00000477657.5	n.541C>G		non_coding_transcript_exon_variant	Exon 5 of 10	2		ENSP00000433347.1
AMY2B	ENST00000491397.1	n.3810C>G		non_coding_transcript_exon_variant	Exon 4 of 9	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.541C>G (p.L181V) alteration is located in exon 6 (coding exon 4) of the AMY2B gene. This alteration results from a C to G substitution at nucleotide position 541, causing the leucine (L) at amino acid position 181 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T;T
Eigen	Benign	0.090
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.92	.;D
M_CAP	Uncertain	0.098	D
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Pathogenic	0.93	D
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.0	N;.
REVEL	Uncertain	0.49
Sift	Benign	0.18	T;.
Sift4G	Benign	0.30	T;T
Polyphen		0.010	B;B
Vest4		0.46
MutPred		0.40		Gain of catalytic residue at L181 (P = 0.1023);Gain of catalytic residue at L181 (P = 0.1023);
MVP		0.79
MPC		0.15
ClinPred		0.59	D
GERP RS		4.7
Varity_R		0.22
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-104116357;