5-35709082-G-C

Variant names:

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.2800G>C(p.Ala934Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 1,613,346 control chromosomes in the GnomAD database, including 487,090 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43326 hom., cov: 31)

Exomes 𝑓: 0.78 ( 443764 hom. )

Consequence

SPEF2
NM_024867.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.47

Publications

25 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:

ENSG00000248969 (HGNC:):

ENSG00000248969 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=2.2953827E-5).

BP6

Variant 5-35709082-G-C is Benign according to our data. Variant chr5-35709082-G-C is described in ClinVar as [Benign]. Clinvar id is 403479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPEF2	NM_024867.4 link	c.2800G>C	p.Ala934Pro	missense_variant	Exon 19 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.2800G>C	p.Ala934Pro	missense_variant	Exon 19 of 37	1	NM_024867.4	ENSP00000348314.3		Q9C093-1

Frequencies

GnomAD3 genomes

AF:

0.752

AC:

114257

AN:

151964

Hom.:

43311

Cov.:

show subpopulations

Gnomad AFR

AF:

0.664

Gnomad AMI

AF:

0.828

Gnomad AMR

AF:

0.774

Gnomad ASJ

AF:

0.787

Gnomad EAS

AF:

0.780

Gnomad SAS

AF:

0.686

Gnomad FIN

AF:

0.782

Gnomad MID

AF:

0.829

Gnomad NFE

AF:

0.794

Gnomad OTH

AF:

0.770

GnomAD2 exomes

AF:

0.755

AC:

187832

AN:

248832

AF XY:

0.758

show subpopulations

Gnomad AFR exome

AF:

0.660

Gnomad AMR exome

AF:

0.681

Gnomad ASJ exome

AF:

0.804

Gnomad EAS exome

AF:

0.776

Gnomad FIN exome

AF:

0.771

Gnomad NFE exome

AF:

0.794

Gnomad OTH exome

AF:

0.772

GnomAD4 exome

AF:

0.778

AC:

1137128

AN:

1461264

Hom.:

443764

Cov.:

AF XY:

0.777

AC XY:

564449

AN XY:

726882

show subpopulations

African (AFR)

AF:

0.663

AC:

22183

AN:

33460

American (AMR)

AF:

0.692

AC:

30897

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.801

AC:

20940

AN:

26134

East Asian (EAS)

AF:

0.799

AC:

31717

AN:

39684

South Asian (SAS)

AF:

0.699

AC:

60207

AN:

86086

European-Finnish (FIN)

AF:

0.769

AC:

41014

AN:

53344

Middle Eastern (MID)

AF:

0.824

AC:

4748

AN:

5764

European-Non Finnish (NFE)

AF:

0.790

AC:

878607

AN:

1111732

Other (OTH)

AF:

0.775

AC:

46815

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

12854

25708

38563

51417

64271

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.752

AC:

114321

AN:

152082

Hom.:

43326

Cov.:

AF XY:

0.752

AC XY:

55934

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.664

AC:

27552

AN:

41474

American (AMR)

AF:

0.774

AC:

11832

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.787

AC:

2731

AN:

3468

East Asian (EAS)

AF:

0.780

AC:

4028

AN:

5164

South Asian (SAS)

AF:

0.685

AC:

3298

AN:

4814

European-Finnish (FIN)

AF:

0.782

AC:

8264

AN:

10562

Middle Eastern (MID)

AF:

0.830

AC:

244

AN:

294

European-Non Finnish (NFE)

AF:

0.794

AC:

53989

AN:

67988

Other (OTH)

AF:

0.771

AC:

1628

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1442

2885

4327

5770

7212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.786

Hom.:

15329

Bravo

AF:

0.744

TwinsUK

AF:

0.791

AC:

2932

ALSPAC

AF:

0.790

AC:

3045

ESP6500AA

AF:

0.672

AC:

2496

ESP6500EA

AF:

0.794

AC:

6506

ExAC

AF:

0.755

AC:

91235

Asia WGS

AF:

0.713

AC:

2479

AN:

3476

EpiCase

AF:

0.800

EpiControl

AF:

0.800

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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 -

Spermatogenic failure 43

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.030

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.0016

.;T;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.32

T;T;T;T

MetaRNN

Benign

0.000023

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.4

.;.;N;.

PhyloP100

-2.5

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.23

N;.;N;N

REVEL

Benign

0.020

Sift

Benign

0.54

T;.;T;T

Sift4G

Benign

0.43

T;.;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.043

MPC

0.034

ClinPred

0.00030

GERP RS

-2.1

Varity_R

0.044

gMVP

0.17

Mutation Taster

=99/1

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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5-35709082-G-C

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