rs34708521

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.1498G>A(p.Asp500Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0753 in 1,609,122 control chromosomes in the GnomAD database, including 6,772 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.085 ( 795 hom., cov: 32)

Exomes 𝑓: 0.074 ( 5977 hom. )

Consequence

SPEF2
NM_024867.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 6.16

Publications

22 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):

spermatogenic failure 43
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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=0.0014680028).

BP6

Variant 5-35670201-G-A is Benign according to our data. Variant chr5-35670201-G-A is described in ClinVar as [Benign]. Clinvar id is 403474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPEF2	NM_024867.4 link	c.1498G>A	p.Asp500Asn	missense_variant	Exon 10 of 37	ENST00000356031.8	NP_079143.3	Q9C093-1A0A140VKD0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPEF2	ENST00000356031.8 link	c.1498G>A	p.Asp500Asn	missense_variant	Exon 10 of 37	1	NM_024867.4	ENSP00000348314.3		Q9C093-1

Frequencies

GnomAD3 genomes

AF:

0.0850

AC:

12905

AN:

151856

Hom.:

793

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0970

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.0447

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.0596

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0568

Gnomad OTH

AF:

0.0885

GnomAD2 exomes

AF:

0.100

AC:

24921

AN:

248672

AF XY:

0.0951

show subpopulations

Gnomad AFR exome

AF:

0.0995

Gnomad AMR exome

AF:

0.167

Gnomad ASJ exome

AF:

0.0500

Gnomad EAS exome

AF:

0.329

Gnomad FIN exome

AF:

0.0643

Gnomad NFE exome

AF:

0.0581

Gnomad OTH exome

AF:

0.0750

GnomAD4 exome

AF:

0.0743

AC:

108213

AN:

1457148

Hom.:

5977

Cov.:

AF XY:

0.0736

AC XY:

53333

AN XY:

724850

show subpopulations

African (AFR)

AF:

0.100

AC:

3339

AN:

33306

American (AMR)

AF:

0.162

AC:

7178

AN:

44286

Ashkenazi Jewish (ASJ)

AF:

0.0480

AC:

1246

AN:

25980

East Asian (EAS)

AF:

0.337

AC:

13298

AN:

39480

South Asian (SAS)

AF:

0.0888

AC:

7600

AN:

85582

European-Finnish (FIN)

AF:

0.0656

AC:

3498

AN:

53354

Middle Eastern (MID)

AF:

0.0440

AC:

253

AN:

5746

European-Non Finnish (NFE)

AF:

0.0602

AC:

66829

AN:

1109196

Other (OTH)

AF:

0.0826

AC:

4972

AN:

60218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

4304

8608

12911

17215

21519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0850

AC:

12914

AN:

151974

Hom.:

795

Cov.:

AF XY:

0.0867

AC XY:

6438

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.0970

AC:

4025

AN:

41496

American (AMR)

AF:

0.123

AC:

1872

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.0447

AC:

155

AN:

3470

East Asian (EAS)

AF:

0.321

AC:

1656

AN:

5164

South Asian (SAS)

AF:

0.101

AC:

488

AN:

4818

European-Finnish (FIN)

AF:

0.0596

AC:

631

AN:

10584

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0568

AC:

3854

AN:

67870

Other (OTH)

AF:

0.0866

AC:

183

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

572

1144

1715

2287

2859

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0720

Hom.:

2130

Bravo

AF:

0.0924

TwinsUK

AF:

0.0653

AC:

242

ALSPAC

AF:

0.0584

AC:

225

ESP6500AA

AF:

0.0994

AC:

438

ESP6500EA

AF:

0.0528

AC:

454

ExAC

AF:

0.0966

AC:

11729

Asia WGS

AF:

0.180

AC:

626

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.070

.;.;T;T;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

D;D;D;D;D

MetaRNN

Benign

0.0015

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

2.0

M;.;.;M;M

PhyloP100

6.2

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.6

D;N;.;N;N

REVEL

Benign

0.17

Sift

Benign

0.26

T;T;.;T;T

Sift4G

Benign

0.40

T;T;.;T;T

Polyphen

1.0

D;D;.;D;.

Vest4

0.11

MPC

0.18

ClinPred

0.014

GERP RS

5.1

Varity_R

0.19

gMVP

0.27

Mutation Taster

=89/11

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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rs34708521

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over