rs10015630

Variant names:

• chr4-56812976-A-G
• rs10015630
• NM_001271718.2:c.250-1182T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-56812976-A-G
• chr4-56812976-A-T

Variant summary

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

The NM_001271718.2(SPINK2):​c.250-1182T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,140 control chromosomes in the GnomAD database, including 41,312 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 0.73 (41312 hom., cov: 32)
• Consequence: SPINK2 NM_001271718.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.862
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271718.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINK2	NM_001271718.2	MANE Select	c.250-1182T>C		intron	N/A	NP_001258647.1	D6RI10
	SPINK2	NM_001271722.2		c.206-2792T>C		intron	N/A	NP_001258651.1	A0A087WTA9
	SPINK2	NM_001271720.2		c.205-1182T>C		intron	N/A	NP_001258649.1	D6RC51

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINK2	ENST00000506738.6	TSL:2 MANE Select	c.250-1182T>C		intron	N/A	ENSP00000425961.1	D6RI10
	SPINK2	ENST00000248701.8	TSL:1	c.100-1182T>C		intron	N/A	ENSP00000248701.4	P20155
	SPINK2	ENST00000618802.3	TSL:3	c.206-2792T>C		intron	N/A	ENSP00000477722.1	A0A087WTA9

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110640 AN: 152022 Hom.: 41251 Cov.: 32

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.728 AC: 110761 AN: 152140 Hom.: 41312 Cov.: 32 AF XY: 0.735 AC XY: 54646 AN XY: 74380

African (AFR) AF: 0.855 AC: 35499 AN: 41516

American (AMR) AF: 0.741 AC: 11316 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2068 AN: 3472

East Asian (EAS) AF: 0.973 AC: 5054 AN: 5192

South Asian (SAS) AF: 0.841 AC: 4056 AN: 4824

European-Finnish (FIN) AF: 0.690 AC: 7297 AN: 10574

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.636 AC: 43225 AN: 67988

Other (OTH) AF: 0.718 AC: 1515 AN: 2110

Alfa AF: 0.680 Hom.: 76633

Bravo AF: 0.737

Asia WGS AF: 0.897 AC: 3115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.54
DANN	Benign	0.38
PhyloP100		-0.86
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: rs10015630; hg19: chr4-57679142;