19-38264308-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000590510.5(SPINT2):c.-44-19319G>A 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 152,102 control chromosomes in the GnomAD database, including 4,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4254 hom., cov: 32)
  • Exomes 𝑓: 0.28 (3 hom.)
• Consequence: SPINT2 ENST00000590510.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.67

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-38264308-G-A is Benign according to our data. Variant chr19-38264308-G-A is described in ClinVar as [Benign]. Clinvar id is 1237272.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPINT2	ENST00000590510.5	c.-44-19319G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35425 AN: 151878 Hom.: 4233 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.219

GnomAD4 exome AF: 0.279 AC: 29 AN: 104 Hom.: 3 AF XY: 0.311 AC XY: 23 AN XY: 74

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.234 AC: 35494 AN: 151998 Hom.: 4254 Cov.: 32 AF XY: 0.235 AC XY: 17437 AN XY: 74282

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.218

Alfa AF: 0.235 Hom.: 657

Bravo AF: 0.242

Asia WGS AF: 0.252 AC: 877 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.23
Dann	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17554832; hg19: chr19-38754948;