19-38264348-G-A

Position:

• chr19-38264348-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.-44-19279G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,190 control chromosomes in the GnomAD database, including 4,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4251 hom., cov: 32)
  • Exomes 𝑓: 0.29 (11 hom.)
• Consequence: SPINT2 ENST00000590510.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.92

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=-0.79).
• BP6: Variant 19-38264348-G-A is Benign according to our data. Variant chr19-38264348-G-A is described in ClinVar as [Benign]. Clinvar id is 1276397.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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINT2	ENST00000590510.5	c.-44-19279G>A		intron_variant	Intron 1 of 2	3		ENSP00000465301.1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35408 AN: 151864 Hom.: 4230 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: 0.218

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.287 AC: 62 AN: 216 Hom.: 11 AF XY: 0.281 AC XY: 45 AN XY: 160

Gnomad4 AFR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.285

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.233 AC: 35474 AN: 151974 Hom.: 4251 Cov.: 32 AF XY: 0.235 AC XY: 17443 AN XY: 74298

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.218

Alfa AF: 0.228 Hom.: 626

Bravo AF: 0.242

Asia WGS AF: 0.249 AC: 864 AN: 3468

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.15
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17554839; hg19: chr19-38754988;