rs7710284

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 links:

ENSG00000248969 (HGNC:):

ENSG00000248969 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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

GnomAD3 exomes

AF:

0.219

AC:

54506

AN:

248760

Hom.:

7746

AF XY:

0.207

AC XY:

27968

AN XY:

135008

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 SAS exome

AF:

0.206

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

Gnomad4 AFR exome

AF:

0.566

Gnomad4 AMR exome

AF:

0.277

Gnomad4 ASJ exome

AF:

0.178

Gnomad4 EAS exome

AF:

0.406

Gnomad4 SAS exome

AF:

0.204

Gnomad4 FIN exome

AF:

0.190

Gnomad4 NFE exome

AF:

0.131

Gnomad4 OTH exome

AF:

0.186

GnomAD4 genome

AF:

0.273

AC:

41551

AN:

151944

Hom.:

8222

Cov.:

AF XY:

0.275

AC XY:

20406

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.551

Gnomad4 AMR

AF:

0.230

Gnomad4 ASJ

AF:

0.168

Gnomad4 EAS

AF:

0.390

Gnomad4 SAS

AF:

0.219

Gnomad4 FIN

AF:

0.189

Gnomad4 NFE

AF:

0.132

Gnomad4 OTH

AF:

0.233

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 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

Benign

0.073

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.068

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over