2-79122104-T-G

Position:

• chr2-79122104-T-G

Variant summary

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

The NM_002909.5(REG1A):​c.300T>G​(p.Ile100Met) 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: 32)
• Consequence: REG1A NM_002909.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.215

Genes affected

REG1A (HGNC:9951): (regenerating family member 1 alpha) This gene is a type I subclass member of the Reg gene family. The Reg gene family is a multigene family grouped into four subclasses, types I, II, III and IV, based on the primary structures of the encoded proteins. This gene encodes a protein that is secreted by the exocrine pancreas. It is associated with islet cell regeneration and diabetogenesis and may be involved in pancreatic lithogenesis. Reg family members REG1B, REGL, PAP and this gene are tandemly clustered on chromosome 2p12 and may have arisen from the same ancestral gene by gene duplication. [provided by RefSeq, Jul 2008]

REG1A (HGNC:):

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/exons	MANE	Protein	UniProt
REG1A	NM_002909.5	c.300T>G	p.Ile100Met	missense_variant	4/6	ENST00000233735.2	NP_002900.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REG1A	ENST00000233735.2	c.300T>G	p.Ile100Met	missense_variant	4/6	1	NM_002909.5	ENSP00000233735.1
REG1A	ENST00000488524.1	n.806T>G		non_coding_transcript_exon_variant	3/3	1
REG1A	ENST00000485184.1	n.327T>G		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2023

The c.300T>G (p.I100M) alteration is located in exon 4 (coding exon 3) of the REG1A gene. This alteration results from a T to G substitution at nucleotide position 300, causing the isoleucine (I) at amino acid position 100 to be replaced by a methionine (M). 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	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Benign	-0.018
Eigen_PC	Benign	-0.080
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0025	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.9	M
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.12
Sift	Benign	0.031	D
Sift4G	Uncertain	0.018	D
Polyphen		0.47	P
Vest4		0.43
MutPred		0.65		Gain of catalytic residue at I100 (P = 0.0193);
MVP		0.19
MPC		0.12
ClinPred		0.61	D
GERP RS		1.1
Varity_R		0.50
gMVP		0.46

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: chr2-79349230;