Genetic Variant SPINK2:c.-7G>C (chr4-56821669-C-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001271718.2(SPINK2):c.-7G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000951 in 1,525,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

SPINK2
NM_001271718.2 5_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.14

Publications

0 publications found

Variant links:

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)

SPINK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 4-56821669-C-G is Benign according to our data. Variant chr4-56821669-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3034488.Status of the report is no_assertion_criteria_provided, 0 stars.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPINK2	NM_001271718.2	MANE Select	c.-7G>C	5_prime_UTR	Exon 1 of 4	NP_001258647.1	D6RI10
SPINK2	NM_001271722.2		c.-7G>C	5_prime_UTR	Exon 1 of 2	NP_001258651.1	A0A087WTA9
SPINK2	NM_001271720.2		c.-7G>C	5_prime_UTR	Exon 1 of 4	NP_001258649.1	D6RC51

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPINK2	ENST00000506738.6	TSL:2 MANE Select	c.-7G>C	5_prime_UTR	Exon 1 of 4	ENSP00000425961.1	D6RI10
SPINK2	ENST00000248701.8	TSL:1	c.-7G>C	5_prime_UTR	Exon 1 of 4	ENSP00000248701.4	P20155
SPINK2	ENST00000618802.3	TSL:3	c.-7G>C	5_prime_UTR	Exon 1 of 2	ENSP00000477722.1	A0A087WTA9

Frequencies

GnomAD3 genomes

AF:

0.0000531

AC:

AN:

150570

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000134

AC:

AN:

119762

AF XY:

0.000122

show subpopulations

Gnomad AFR exome

AF:

0.000198

Gnomad AMR exome

AF:

0.0000968

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000997

AC:

137

AN:

1374706

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

677886

show subpopulations

African (AFR)

AF:

0.0000335

AC:

AN:

29818

American (AMR)

AF:

0.0000897

AC:

AN:

33430

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24540

East Asian (EAS)

AF:

0.00

AC:

AN:

34062

South Asian (SAS)

AF:

0.000311

AC:

AN:

77240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42788

Middle Eastern (MID)

AF:

0.000212

AC:

AN:

4706

European-Non Finnish (NFE)

AF:

0.0000980

AC:

105

AN:

1071004

Other (OTH)

AF:

0.0000525

AC:

AN:

57118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000531

AC:

AN:

150570

Hom.:

Cov.:

AF XY:

0.0000544

AC XY:

AN XY:

73530

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40264

American (AMR)

AF:

0.00

AC:

AN:

14948

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000152

Hom.:

Bravo

AF:

0.0000453

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

SPINK2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.5

(source)

DANN

Benign

0.62

PhyloP100

-1.1

PromoterAI

-0.029

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over