2-79123164-G-A

Position:

• chr2-79123164-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_002909.5(REG1A):​c.450G>A​(p.Lys150Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00484 in 1,612,290 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0049 (34 hom.)
• Consequence: REG1A NM_002909.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.90

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 Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-79123164-G-A is Benign according to our data. Variant chr2-79123164-G-A is described in ClinVar as [Benign]. Clinvar id is 718409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.9 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REG1A	NM_002909.5	c.450G>A	p.Lys150Lys	synonymous_variant	6/6	ENST00000233735.2	NP_002900.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REG1A	ENST00000233735.2	c.450G>A	p.Lys150Lys	synonymous_variant	6/6	1	NM_002909.5	ENSP00000233735.1

Frequencies

GnomAD3 genomes AF: 0.00384 AC: 585 AN: 152214 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0133

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00551

Gnomad OTH AF: 0.00525

GnomAD3 exomes AF: 0.00377 AC: 941 AN: 249726 Hom.: 7 AF XY: 0.00347 AC XY: 468 AN XY: 135004

Gnomad AFR exome AF: 0.000678

Gnomad AMR exome AF: 0.000760

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000165

Gnomad FIN exome AF: 0.0140

Gnomad NFE exome AF: 0.00507

Gnomad OTH exome AF: 0.00396

GnomAD4 exome AF: 0.00495 AC: 7220 AN: 1459958 Hom.: 34 Cov.: 30 AF XY: 0.00477 AC XY: 3465 AN XY: 726268

Gnomad4 AFR exome AF: 0.000359

Gnomad4 AMR exome AF: 0.000922

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.0168

Gnomad4 NFE exome AF: 0.00542

Gnomad4 OTH exome AF: 0.00386

GnomAD4 genome AF: 0.00384 AC: 585 AN: 152332 Hom.: 2 Cov.: 33 AF XY: 0.00379 AC XY: 282 AN XY: 74484

Gnomad4 AFR AF: 0.000794

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0133

Gnomad4 NFE AF: 0.00551

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00421 Hom.: 2

Bravo AF: 0.00272

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00387

EpiControl AF: 0.00445

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.23
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs144307810; hg19: chr2-79350290;