Genetic Variant SPINT2:c.-44-19175C>G (chr19-38264452-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0880

Variant links:

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]

SPINT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
SPINT2	NM_021102.4 link	c.-441C>G		upstream_gene_variant		ENST00000301244.12	NP_066925.1	O43291-1
SPINT2	NM_001166103.2 link	c.-441C>G		upstream_gene_variant			NP_001159575.1	O43291-2A0A140VJV6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINT2	ENST00000301244.12 link	c.-441C>G		upstream_gene_variant		1	NM_021102.4	ENSP00000301244.5		O43291-1

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35469

AN:

151784

Hom.:

4236

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.182

AC XY:

AN XY:

500

show subpopulations

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.:

AF XY:

0.235

AC XY:

17470

AN XY:

74272

show subpopulations

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.:

Bravo

AF:

0.242

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over