2-44320097-G-C

Position:

• chr2-44320097-G-C

Variant summary

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

The NM_001171613.2(PREPL):​c.*1259C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,025,554 control chromosomes in the GnomAD database, including 826 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (499 hom., cov: 33)
  • Exomes 𝑓: 0.0049 (327 hom.)
• Consequence: PREPL NM_001171613.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.319

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=-0.86).
• BP6: Variant 2-44320097-G-C is Benign according to our data. Variant chr2-44320097-G-C is described in ClinVar as [Benign]. Clinvar id is 1242368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PREPL	NM_001171613.2	c.*1259C>G		3_prime_UTR_variant	14/14	ENST00000409411.6	NP_001165084.1
SLC3A1	NM_000341.4	c.1618-102G>C		intron_variant		ENST00000260649.11	NP_000332.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PREPL	ENST00000409411.6	c.*1259C>G		3_prime_UTR_variant	14/14	1	NM_001171613.2	ENSP00000387095	P4
SLC3A1	ENST00000260649.11	c.1618-102G>C		intron_variant		1	NM_000341.4	ENSP00000260649	P1

Frequencies

GnomAD3 genomes AF: 0.0453 AC: 6886 AN: 152072 Hom.: 491 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0161

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000661

Gnomad OTH AF: 0.0311

GnomAD4 exome AF: 0.00485 AC: 4238 AN: 873364 Hom.: 327 Cov.: 12 AF XY: 0.00421 AC XY: 1876 AN XY: 446128

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.00931

Gnomad4 ASJ exome AF: 0.00118

Gnomad4 EAS exome AF: 0.0000300

Gnomad4 SAS exome AF: 0.000265

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000262

Gnomad4 OTH exome AF: 0.0111

GnomAD4 genome AF: 0.0455 AC: 6918 AN: 152190 Hom.: 499 Cov.: 33 AF XY: 0.0441 AC XY: 3280 AN XY: 74402

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0160

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000662

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.0365 Hom.: 45

Bravo AF: 0.0515

Asia WGS AF: 0.0100 AC: 36 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	Dec 01, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs17032122; hg19: chr2-44547236;