rs781542

Variant names:

• chr4-56821138-A-G
• rs781542
• NM_001271718.2:c.205+320T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001271718.2(SPINK2):​c.205+320T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 152,094 control chromosomes in the GnomAD database, including 19,386 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (19386 hom., cov: 33)
• Consequence: SPINK2 NM_001271718.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289
• Publications: 5 publications found

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]

SPINK2 Gene-Disease associations (from GenCC):

• spermatogenic failure 29

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPINK2	NM_001271718.2	c.205+320T>C		intron_variant	Intron 1 of 3	ENST00000506738.6	NP_001258647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINK2	ENST00000506738.6	c.205+320T>C		intron_variant	Intron 1 of 3	2	NM_001271718.2	ENSP00000425961.1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73352 AN: 151976 Hom.: 19336 Cov.: 33

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.463

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.483 AC: 73463 AN: 152094 Hom.: 19386 Cov.: 33 AF XY: 0.483 AC XY: 35890 AN XY: 74356

African (AFR) AF: 0.707 AC: 29322 AN: 41498

American (AMR) AF: 0.480 AC: 7335 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1406 AN: 3470

East Asian (EAS) AF: 0.373 AC: 1929 AN: 5168

South Asian (SAS) AF: 0.544 AC: 2622 AN: 4822

European-Finnish (FIN) AF: 0.359 AC: 3799 AN: 10574

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.377 AC: 25631 AN: 67968

Other (OTH) AF: 0.466 AC: 984 AN: 2110

Alfa AF: 0.420 Hom.: 46206

Bravo AF: 0.504

Asia WGS AF: 0.483 AC: 1679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.3
DANN	Benign	0.32
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs781542; hg19: chr4-57687304;