2-79121564-C-G

Variant names:

• chr2-79121564-C-G
• NM_002909.5:c.67C>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_002909.5(REG1A):​c.67C>G​(p.Gln23Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: REG1A NM_002909.5 missense, splice_region
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.43

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035911262).
• BP6: Variant 2-79121564-C-G is Benign according to our data. Variant chr2-79121564-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3788135.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REG1A	NM_002909.5	c.67C>G	p.Gln23Glu	missense_variant, splice_region_variant	Exon 3 of 6	ENST00000233735.2	NP_002900.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REG1A	ENST00000233735.2	c.67C>G	p.Gln23Glu	missense_variant, splice_region_variant	Exon 3 of 6	1	NM_002909.5	ENSP00000233735.1
REG1A	ENST00000461579.1	n.439C>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 2	1
REG1A	ENST00000488524.1	n.266C>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 3	1
REG1A	ENST00000485184.1	n.94C>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461326 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727008

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 22, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.096
DANN	Benign	0.13
DEOGEN2	Benign	0.094	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0048	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.28	N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.90	N
REVEL	Benign	0.049
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.15
MutPred		0.29		Gain of sheet (P = 0.0149);
MVP		0.26
MPC		0.13
ClinPred		0.044	T
GERP RS		-0.055
Varity_R		0.16
gMVP		0.22

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: chr2-79348690;