Variant 5-35641517-A-G 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.248A>G(p.His83Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00201 in 1,613,866 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 15 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 98 hom. )

Consequence

SPEF2
NM_024867.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.14

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=0.002318412).

BP6

Variant 5-35641517-A-G is Benign according to our data. Variant chr5-35641517-A-G is described in ClinVar as [Benign]. Clinvar id is 1182550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPEF2	NM_024867.4 linkuse as main transcript	c.248A>G	p.His83Arg	missense_variant	3/37	ENST00000356031.8	NP_079143.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPEF2	ENST00000356031.8 linkuse as main transcript	c.248A>G	p.His83Arg	missense_variant	3/37	1	NM_024867.4	ENSP00000348314	P2	Q9C093-1

Frequencies

GnomAD3 genomes

AF:

0.00398

AC:

605

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0374

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00911

GnomAD3 exomes

AF:

0.00810

AC:

2036

AN:

251216

Hom.:

AF XY:

0.00625

AC XY:

849

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00506

GnomAD4 exome

AF:

0.00180

AC:

2634

AN:

1461588

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

1123

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.0564

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.00401

AC:

611

AN:

152278

Hom.:

Cov.:

AF XY:

0.00436

AC XY:

325

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.0378

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00901

Alfa

AF:

0.000391

Hom.:

Bravo

AF:

0.00775

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00562

AC:

682

Asia WGS

AF:

0.00144

AC:

AN:

3478

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 05, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.0042

.;.;T;T;.;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.099

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.77

T;T;T;T;T;T

MetaRNN

Benign

0.0023

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.;.;L;.;L

MutationTaster

Benign

0.98

N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.1

N;N;.;N;N;N

REVEL

Benign

0.077

Sift

Benign

0.81

T;T;.;T;T;T

Sift4G

Benign

0.76

T;T;.;T;T;T

Polyphen

0.0020

B;B;.;B;.;.

Vest4

0.12

MVP

0.072

MPC

0.050

ClinPred

0.045

GERP RS

4.8

Varity_R

0.12

gMVP

0.23

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