Variant 5-35646682-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_024867.4(SPEF2):c.601A>G(p.Arg201Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00793 in 1,613,660 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 110 hom. )

Consequence

SPEF2
NM_024867.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.02

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059509277).

BP6

Variant 5-35646682-A-G is Benign according to our data. Variant chr5-35646682-A-G is described in ClinVar as [Benign]. Clinvar id is 3024771.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00587 (894/152346) while in subpopulation SAS AF= 0.0313 (151/4832). AF 95% confidence interval is 0.0272. There are 6 homozygotes in gnomad4. There are 451 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPEF2	NM_024867.4 linkuse as main transcript	c.601A>G	p.Arg201Gly	missense_variant	5/37	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.601A>G	p.Arg201Gly	missense_variant	5/37	1	NM_024867.4	ENSP00000348314	P2	Q9C093-1

Frequencies

GnomAD3 genomes

AF:

0.00586

AC:

892

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00916

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.0312

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00747

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00880

AC:

2203

AN:

250368

Hom.:

AF XY:

0.0104

AC XY:

1411

AN XY:

135324

show subpopulations

Gnomad AFR exome

AF:

0.000925

Gnomad AMR exome

AF:

0.00655

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0332

Gnomad FIN exome

AF:

0.00180

Gnomad NFE exome

AF:

0.00731

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.00814

AC:

11896

AN:

1461314

Hom.:

110

Cov.:

AF XY:

0.00901

AC XY:

6547

AN XY:

726962

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00660

Gnomad4 ASJ exome

AF:

0.00207

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0339

Gnomad4 FIN exome

AF:

0.00200

Gnomad4 NFE exome

AF:

0.00706

Gnomad4 OTH exome

AF:

0.00765

GnomAD4 genome

AF:

0.00587

AC:

894

AN:

152346

Hom.:

Cov.:

AF XY:

0.00605

AC XY:

451

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00915

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0313

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00748

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00698

Hom.:

Bravo

AF:

0.00606

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00768

AC:

ExAC

AF:

0.00886

AC:

1076

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.00938

EpiControl

AF:

0.00824

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

SPEF2: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

.;.;T;T;.;.

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

D;D;D;D;D;D

MetaRNN

Benign

0.0060

T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.6

M;.;.;M;.;M

MutationTaster

Benign

0.98

D;D;D;D

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-4.0

D;D;.;D;D;N

REVEL

Benign

0.13

Sift

Uncertain

0.0070

D;D;.;D;D;D

Sift4G

Uncertain

0.011

D;D;.;D;D;D

Polyphen

1.0

D;D;.;D;.;.

Vest4

0.67

MVP

0.28

MPC

0.060

ClinPred

0.023

GERP RS

5.8

Varity_R

0.26

gMVP

0.35

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