Variant 5-35641489-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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:

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=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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPEF2	NM_024867.4 link	c.220G>A	p.Gly74Ser	missense_variant	Exon 3 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.220G>A	p.Gly74Ser	missense_variant	Exon 3 of 37	1	NM_024867.4	ENSP00000348314.3		Q9C093-1

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

GnomAD3 exomes

AF:

0.0513

AC:

12881

AN:

251194

Hom.:

358

AF XY:

0.0487

AC XY:

6614

AN XY:

135764

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 SAS exome

AF:

0.0264

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

Gnomad4 AFR exome

AF:

0.0603

Gnomad4 AMR exome

AF:

0.0548

Gnomad4 ASJ exome

AF:

0.0359

Gnomad4 EAS exome

AF:

0.00103

Gnomad4 SAS exome

AF:

0.0251

Gnomad4 FIN exome

AF:

0.0920

Gnomad4 NFE exome

AF:

0.0514

Gnomad4 OTH exome

AF:

0.0441

GnomAD4 genome

AF:

0.0539

AC:

8190

AN:

152084

Hom.:

253

Cov.:

AF XY:

0.0544

AC XY:

4044

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0627

Gnomad4 AMR

AF:

0.0423

Gnomad4 ASJ

AF:

0.0375

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.0310

Gnomad4 FIN

AF:

0.0961

Gnomad4 NFE

AF:

0.0518

Gnomad4 OTH

AF:

0.0437

Alfa

AF:

0.0458

Hom.:

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

.;.;T;T;.;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.83

T;T;T;T;T;T

MetaRNN

Benign

0.0031

T;T;T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.5

M;.;.;M;.;M

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.5

N;D;.;N;N;N

REVEL

Benign

0.097

Sift

Benign

0.22

T;T;.;T;T;T

Sift4G

Benign

0.10

T;T;.;D;D;D

Polyphen

0.57

P;P;.;D;.;.

Vest4

0.55

MPC

0.23

ClinPred

0.046

GERP RS

5.1

Varity_R

0.28

gMVP

0.42

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