rs34307272

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024867.4(SPEF2):c.220G>A(p.Gly74Ser) variant causes a missense change. The variant allele was found at a frequency of 0.05 in 1,613,610 control chromosomes in the GnomAD database, including 2,246 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G74C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.054 ( 253 hom., cov: 32)

Exomes 𝑓: 0.050 ( 1993 hom. )

Consequence

SPEF2
NM_024867.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.91

Publications

9 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: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
non-syndromic male infertility due to sperm motility disorder
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SPEF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030751526).

BP6

Variant 5-35641489-G-A is Benign according to our data. Variant chr5-35641489-G-A is described in ClinVar as Benign. ClinVar VariationId is 1270915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0606 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.220G>A	p.Gly74Ser	missense	Exon 3 of 37	NP_079143.3
	SPEF2	NM_144722.4		c.220G>A	p.Gly74Ser	missense	Exon 3 of 10	NP_653323.1	Q9C093-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPEF2	ENST00000356031.8	TSL:1 MANE Select	c.220G>A	p.Gly74Ser	missense	Exon 3 of 37	ENSP00000348314.3	Q9C093-1
SPEF2	ENST00000509059.5	TSL:1	c.220G>A	p.Gly74Ser	missense	Exon 3 of 19	ENSP00000421593.1	D6REZ4
SPEF2	ENST00000282469.10	TSL:1	c.220G>A	p.Gly74Ser	missense	Exon 3 of 10	ENSP00000282469.6	Q9C093-3

Frequencies

GnomAD3 genomes

AF:

0.0538

AC:

8182

AN:

151966

Hom.:

253

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0626

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0424

Gnomad ASJ

AF:

0.0375

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.0314

Gnomad FIN

AF:

0.0961

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0518

Gnomad OTH

AF:

0.0437

GnomAD2 exomes

AF:

0.0513

AC:

12881

AN:

251194

AF XY:

0.0487

show subpopulations

Gnomad AFR exome

AF:

0.0657

Gnomad AMR exome

AF:

0.0547

Gnomad ASJ exome

AF:

0.0380

Gnomad EAS exome

AF:

0.00228

Gnomad FIN exome

AF:

0.0947

Gnomad NFE exome

AF:

0.0559

Gnomad OTH exome

AF:

0.0478

GnomAD4 exome

AF:

0.0496

AC:

72460

AN:

1461526

Hom.:

1993

Cov.:

AF XY:

0.0486

AC XY:

35345

AN XY:

727076

show subpopulations

African (AFR)

AF:

0.0603

AC:

2018

AN:

33458

American (AMR)

AF:

0.0548

AC:

2450

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.0359

AC:

938

AN:

26116

East Asian (EAS)

AF:

0.00103

AC:

AN:

39688

South Asian (SAS)

AF:

0.0251

AC:

2167

AN:

86246

European-Finnish (FIN)

AF:

0.0920

AC:

4912

AN:

53406

Middle Eastern (MID)

AF:

0.0231

AC:

133

AN:

5766

European-Non Finnish (NFE)

AF:

0.0514

AC:

57141

AN:

1111788

Other (OTH)

AF:

0.0441

AC:

2660

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

3655

7310

10965

14620

18275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2156

4312

6468

8624

10780

<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:

0.0539

AC:

8190

AN:

152084

Hom.:

253

Cov.:

AF XY:

0.0544

AC XY:

4044

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0627

AC:

2599

AN:

41480

American (AMR)

AF:

0.0423

AC:

646

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0375

AC:

130

AN:

3470

East Asian (EAS)

AF:

0.00193

AC:

AN:

5172

South Asian (SAS)

AF:

0.0310

AC:

149

AN:

4812

European-Finnish (FIN)

AF:

0.0961

AC:

1016

AN:

10572

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0518

AC:

3522

AN:

67994

Other (OTH)

AF:

0.0437

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

406

813

1219

1626

2032

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<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:

0.0501

Hom.:

420

Bravo

AF:

0.0502

TwinsUK

AF:

0.0504

AC:

187

ALSPAC

AF:

0.0535

AC:

206

ESP6500AA

AF:

0.0667

AC:

294

ESP6500EA

AF:

0.0519

AC:

446

ExAC

AF:

0.0530

AC:

6440

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.0481

EpiControl

AF:

0.0446

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.83

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.5

PhyloP100

3.9

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.097

Sift

Benign

0.22

Sift4G

Benign

0.10

Polyphen

0.57

Vest4

0.55

MPC

0.23

ClinPred

0.046

GERP RS

5.1

Varity_R

0.28

gMVP

0.42

Mutation Taster

=85/15

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over