dbSNP rs10042632: SPEF2:c.2399-1311A>T (chr5-35703243-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024867.4(SPEF2):c.2399-1311A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,740 control chromosomes in the GnomAD database, including 22,267 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 0.54 ( 22267 hom., cov: 31)

Consequence

SPEF2
NM_024867.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.64

Publications

1 publications found

Variant links:

Genes affected

SPEF2 (HGNC:26293): (sperm flagellar 2) Involved in sperm axoneme assembly. Located in sperm flagellum. Implicated in spermatogenic failure 43. [provided by Alliance of Genome Resources, Apr 2022]

SPEF2 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia
Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
spermatogenic failure 43
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
non-syndromic male infertility due to sperm motility disorder
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SPEF2 links:

ENSG00000248969 (HGNC:59028):

ENSG00000248969 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_024867.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024867.4. 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
	SPEF2	NM_024867.4	MANE Select	c.2399-1311A>T		intron	N/A	NP_079143.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPEF2	ENST00000356031.8	TSL:1 MANE Select	c.2399-1311A>T	intron	N/A	ENSP00000348314.3	Q9C093-1
SPEF2	ENST00000509059.5	TSL:1	c.2384-1311A>T	intron	N/A	ENSP00000421593.1	D6REZ4
SPEF2	ENST00000637569.1	TSL:5	c.2399-1311A>T	intron	N/A	ENSP00000490886.1	A0A1B0GWD8

Frequencies

GnomAD3 genomes

AF:

0.537

AC:

81357

AN:

151622

Hom.:

22248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.560

Gnomad AMI

AF:

0.556

Gnomad AMR

AF:

0.454

Gnomad ASJ

AF:

0.562

Gnomad EAS

AF:

0.262

Gnomad SAS

AF:

0.434

Gnomad FIN

AF:

0.620

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.555

Gnomad OTH

AF:

0.530

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

GnomAD4 genome

AF:

0.537

AC:

81423

AN:

151740

Hom.:

22267

Cov.:

AF XY:

0.536

AC XY:

39731

AN XY:

74102

show subpopulations

African (AFR)

AF:

0.560

AC:

23146

AN:

41334

American (AMR)

AF:

0.453

AC:

6896

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.562

AC:

1950

AN:

3470

East Asian (EAS)

AF:

0.263

AC:

1355

AN:

5158

South Asian (SAS)

AF:

0.433

AC:

2086

AN:

4814

European-Finnish (FIN)

AF:

0.620

AC:

6519

AN:

10510

Middle Eastern (MID)

AF:

0.534

AC:

156

AN:

292

European-Non Finnish (NFE)

AF:

0.555

AC:

37684

AN:

67922

Other (OTH)

AF:

0.532

AC:

1125

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1875

3751

5626

7502

9377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

706

1412

2118

2824

3530

<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:

0.553

Hom.:

2961

Bravo

AF:

0.525

Asia WGS

AF:

0.401

AC:

1396

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.36

(source)

DANN

Benign

0.27

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over