rs7710284

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.1848T>A(p.Asn616Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,612,792 control chromosomes in the GnomAD database, including 33,137 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 0.27 ( 8222 hom., cov: 32)

Exomes 𝑓: 0.16 ( 24915 hom. )

Consequence

SPEF2
NM_024867.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.395

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:

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=1.6021313E-5).

BP6

Variant 5-35692673-T-A is Benign according to our data. Variant chr5-35692673-T-A is described in ClinVar as [Benign]. Clinvar id is 403475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPEF2	NM_024867.4 link	c.1848T>A	p.Asn616Lys	missense_variant	Exon 12 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.1848T>A	p.Asn616Lys	missense_variant	Exon 12 of 37	1	NM_024867.4	ENSP00000348314.3		Q9C093-1

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41450

AN:

151826

Hom.:

8182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.550

Gnomad AMI

AF:

0.0703

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.390

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.233

GnomAD2 exomes

AF:

0.219

AC:

54506

AN:

248760

AF XY:

0.207

show subpopulations

Gnomad AFR exome

AF:

0.563

Gnomad AMR exome

AF:

0.285

Gnomad ASJ exome

AF:

0.181

Gnomad EAS exome

AF:

0.399

Gnomad FIN exome

AF:

0.192

Gnomad NFE exome

AF:

0.138

Gnomad OTH exome

AF:

0.182

GnomAD4 exome

AF:

0.163

AC:

237833

AN:

1460848

Hom.:

24915

Cov.:

AF XY:

0.162

AC XY:

117633

AN XY:

726778

show subpopulations

African (AFR)

AF:

0.566

AC:

18910

AN:

33410

American (AMR)

AF:

0.277

AC:

12374

AN:

44614

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

4643

AN:

26102

East Asian (EAS)

AF:

0.406

AC:

16080

AN:

39642

South Asian (SAS)

AF:

0.204

AC:

17599

AN:

86124

European-Finnish (FIN)

AF:

0.190

AC:

10146

AN:

53360

Middle Eastern (MID)

AF:

0.175

AC:

1008

AN:

5764

European-Non Finnish (NFE)

AF:

0.131

AC:

145880

AN:

1111494

Other (OTH)

AF:

0.186

AC:

11193

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

8796

17591

26387

35182

43978

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.273

AC:

41551

AN:

151944

Hom.:

8222

Cov.:

AF XY:

0.275

AC XY:

20406

AN XY:

74238

show subpopulations

African (AFR)

AF:

0.551

AC:

22835

AN:

41444

American (AMR)

AF:

0.230

AC:

3505

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

585

AN:

3472

East Asian (EAS)

AF:

0.390

AC:

2007

AN:

5150

South Asian (SAS)

AF:

0.219

AC:

1054

AN:

4808

European-Finnish (FIN)

AF:

0.189

AC:

1990

AN:

10548

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.132

AC:

8977

AN:

67956

Other (OTH)

AF:

0.233

AC:

491

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1317

2633

3950

5266

6583

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.175

Hom.:

1037

Bravo

AF:

0.291

TwinsUK

AF:

0.131

AC:

486

ALSPAC

AF:

0.130

AC:

502

ESP6500AA

AF:

0.549

AC:

2023

ESP6500EA

AF:

0.131

AC:

1069

ExAC

AF:

0.222

AC:

26795

Asia WGS

AF:

0.306

AC:

1066

AN:

3478

EpiCase

AF:

0.132

EpiControl

AF:

0.124

ClinVar

Significance: Benign

Submissions summary: Benign:3

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.068

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.0025

.;T;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0010

LIST_S2

Benign

0.11

T;T;T;T

MetaRNN

Benign

0.000016

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.90

.;.;N;N

PhyloP100

-0.40

PrimateAI

Benign

0.25

PROVEAN

Benign

0.32

N;.;N;N

REVEL

Benign

0.0010

Sift

Benign

0.89

T;.;T;T

Sift4G

Benign

0.87

T;.;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.016

MutPred

0.22

Gain of ubiquitination at N616 (P = 0.0014);Gain of ubiquitination at N616 (P = 0.0014);Gain of ubiquitination at N616 (P = 0.0014);Gain of ubiquitination at N616 (P = 0.0014);

MPC

0.032

ClinPred

0.0042

GERP RS

-3.6

Varity_R

0.034

gMVP

0.17

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

Publications

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rs7710284

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