2-79120917-A-G

Variant names:

• chr2-79120917-A-G
• rs939433347
• NM_002909.5:c.56A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002909.5(REG1A):​c.56A>G​(p.Gln19Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q19E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: REG1A NM_002909.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.785
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06738281).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002909.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REG1A	NM_002909.5	MANE Select	c.56A>G	p.Gln19Arg	missense	Exon 2 of 6	NP_002900.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REG1A	ENST00000233735.2	TSL:1 MANE Select	c.56A>G	p.Gln19Arg	missense	Exon 2 of 6	ENSP00000233735.1	P05451
	REG1A	ENST00000461579.1	TSL:1	n.428A>G		non_coding_transcript_exon	Exon 1 of 2
	REG1A	ENST00000488524.1	TSL:1	n.255A>G		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461122 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726872

African (AFR) AF: 0.0000598 AC: 2 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111500

Other (OTH) AF: 0.00 AC: 0 AN: 60350

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	1.6
DANN	Benign	0.68
DEOGEN2	Benign	0.23	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0097	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.79
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.049
Sift	Benign	0.18	T
Sift4G	Benign	0.35	T
Polyphen		0.031	B
Vest4		0.13
MutPred		0.32		Loss of sheet (P = 0.0126)
MVP		0.23
MPC		0.12
ClinPred		0.11	T
GERP RS		-6.3
PromoterAI		0.040	Neutral
Varity_R		0.057
gMVP		0.22
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs939433347; hg19: chr2-79348043; COSMIC: COSV99286897;