2-44319992-A-G

Position:

• chr2-44319992-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000409411.6(PREPL):​c.*1364T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 566,202 control chromosomes in the GnomAD database, including 122,783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (32979 hom., cov: 32)
  • Exomes 𝑓: 0.65 (89804 hom.)
• Consequence: PREPL ENST00000409411.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.483

Genes affected

PREPL (HGNC:30228): (prolyl endopeptidase like) The protein encoded by this gene belongs to the prolyl oligopeptidase subfamily of serine peptidases. Mutations in this gene have been associated with hypotonia-cystinuria syndrome, also known as the 2p21 deletion syndrome. Several alternatively spliced transcript variants encoding either the same or different isoforms have been described for this gene.[provided by RefSeq, Jan 2010]

SLC3A1 (HGNC:11025): (solute carrier family 3 member 1) This gene encodes a type II membrane glycoprotein which is one of the components of the renal amino acid transporter which transports neutral and basic amino acids in the renal tubule and intestinal tract. Mutations and deletions in this gene are associated with cystinuria. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 2-44319992-A-G is Benign according to our data. Variant chr2-44319992-A-G is described in ClinVar as [Benign]. Clinvar id is 1291996.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PREPL	NM_001171613.2	c.*1364T>C		3_prime_UTR_variant	14/14	ENST00000409411.6	NP_001165084.1
SLC3A1	NM_000341.4	c.1618-207A>G		intron_variant		ENST00000260649.11	NP_000332.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PREPL	ENST00000409411.6	c.*1364T>C		3_prime_UTR_variant	14/14	1	NM_001171613.2	ENSP00000387095	P4
SLC3A1	ENST00000260649.11	c.1618-207A>G		intron_variant		1	NM_000341.4	ENSP00000260649	P1

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99306 AN: 151966 Hom.: 32973 Cov.: 32

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.655

GnomAD4 exome AF: 0.652 AC: 270193 AN: 414118 Hom.: 89804 Cov.: 3 AF XY: 0.655 AC XY: 144854 AN XY: 221070

Gnomad4 AFR exome AF: 0.680

Gnomad4 AMR exome AF: 0.583

Gnomad4 ASJ exome AF: 0.696

Gnomad4 EAS exome AF: 0.372

Gnomad4 SAS exome AF: 0.666

Gnomad4 FIN exome AF: 0.611

Gnomad4 NFE exome AF: 0.686

Gnomad4 OTH exome AF: 0.648

GnomAD4 genome AF: 0.653 AC: 99354 AN: 152084 Hom.: 32979 Cov.: 32 AF XY: 0.644 AC XY: 47847 AN XY: 74332

Gnomad4 AFR AF: 0.677

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.651

Alfa AF: 0.642 Hom.: 5554

Bravo AF: 0.651

Asia WGS AF: 0.501 AC: 1748 AN: 3478

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	GeneDx	Aug 20, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.6
DANN	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs2289462; hg19: chr2-44547131;