19-38264452-C-G

Position:

• chr19-38264452-C-G

Variant summary

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

The ENST00000590510.5(SPINT2):​c.-44-19175C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,702 control chromosomes in the GnomAD database, including 4,272 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4258 hom., cov: 33)
  • Exomes 𝑓: 0.19 (14 hom.)
• Consequence: SPINT2 ENST00000590510.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0880

Genes affected

SPINT2 (HGNC:11247): (serine peptidase inhibitor, Kunitz type 2) This gene encodes a transmembrane protein with two extracellular Kunitz domains that inhibits a variety of serine proteases. The protein inhibits HGF activator which prevents the formation of active hepatocyte growth factor. This gene is a putative tumor suppressor, and mutations in this gene result in congenital sodium diarrhea. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 19-38264452-C-G is Benign according to our data. Variant chr19-38264452-C-G is described in ClinVar as [Benign]. Clinvar id is 1286126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINT2	ENST00000590510.5	c.-44-19175C>G		intron_variant	Intron 1 of 2	3		ENSP00000465301.1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35469 AN: 151784 Hom.: 4236 Cov.: 33

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.188 AC: 151 AN: 804 Hom.: 14 Cov.: 0 AF XY: 0.182 AC XY: 91 AN XY: 500

Gnomad4 AFR exome AF: 0.0769

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.300

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.204

Gnomad4 FIN exome AF: 0.227

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.136

GnomAD4 genome AF: 0.234 AC: 35538 AN: 151898 Hom.: 4258 Cov.: 33 AF XY: 0.235 AC XY: 17470 AN XY: 74272

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.219

Alfa AF: 0.0739 Hom.: 90

Bravo AF: 0.242

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	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.1
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17526168; hg19: chr19-38755092;