NM_001271718.2:c.250-1182T>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001271718.2(SPINK2):​c.250-1182T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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>A		intron	N/A	NP_001258647.1	D6RI10
	SPINK2	NM_001271722.2		c.206-2792T>A		intron	N/A	NP_001258651.1	A0A087WTA9
	SPINK2	NM_001271720.2		c.205-1182T>A		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>A		intron	N/A	ENSP00000425961.1	D6RI10
	SPINK2	ENST00000248701.8	TSL:1	c.100-1182T>A		intron	N/A	ENSP00000248701.4	P20155
	SPINK2	ENST00000618802.3	TSL:3	c.206-2792T>A		intron	N/A	ENSP00000477722.1	A0A087WTA9

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 76633

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.45
DANN	Benign	0.68
PhyloP100		-0.86

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;