4-56809985-C-CT

Variant names:

• chr4-56809985-C-CT
• rs150309687
• ENST00000506738:c.*153dupA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_001271722.2(SPINK2):​c.404dupA​(p.Ter135fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,500,592 control chromosomes in the GnomAD database, including 26 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0067 (14 hom., cov: 32)
  • Exomes 𝑓: 0.00094 (12 hom.)
• Consequence: SPINK2 NM_001271722.2 frameshift
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.375

Genes affected

SPINK2 (HGNC:11245): (serine peptidase inhibitor Kazal type 2) This gene encodes a member of the family of serine protease inhibitors of the Kazal type (SPINK). The encoded protein acts as a trypsin and acrosin inhibitor in the genital tract and is localized in the spermatozoa. The protein has been associated with the progression of lymphomas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 4-56809985-C-CT is Benign according to our data. Variant chr4-56809985-C-CT is described in ClinVar as [Benign]. Clinvar id is 3055956.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00666 (1014/152190) while in subpopulation AFR AF= 0.0224 (928/41520). AF 95% confidence interval is 0.0212. There are 14 homozygotes in gnomad4. There are 478 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPINK2	NM_001271718.2	c.*153dupA		3_prime_UTR_variant	Exon 4 of 4	ENST00000506738.6	NP_001258647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINK2	ENST00000506738	c.*153dupA		3_prime_UTR_variant	Exon 4 of 4	2	NM_001271718.2	ENSP00000425961.1

Frequencies

GnomAD3 genomes AF: 0.00667 AC: 1015 AN: 152072 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0224

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00708

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.000935 AC: 1261 AN: 1348402 Hom.: 12 Cov.: 30 AF XY: 0.00103 AC XY: 684 AN XY: 663834

Gnomad4 AFR exome AF: 0.0225

Gnomad4 AMR exome AF: 0.00192

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00591

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000404

Gnomad4 OTH exome AF: 0.00227

GnomAD4 genome AF: 0.00666 AC: 1014 AN: 152190 Hom.: 14 Cov.: 32 AF XY: 0.00643 AC XY: 478 AN XY: 74392

Gnomad4 AFR AF: 0.0224

Gnomad4 AMR AF: 0.00282

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00708

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00144 Hom.: 0

Bravo AF: 0.00753

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SPINK2-related disorder Benign:1

May 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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: rs150309687; hg19: chr4-57676151;