Variant rs34708521 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.1498G>A(p.Asp500Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0753 in 1,609,122 control chromosomes in the GnomAD database, including 6,772 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.085 ( 795 hom., cov: 32)

Exomes 𝑓: 0.074 ( 5977 hom. )

Consequence

SPEF2
NM_024867.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.16

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:

SPEF2 (HGNC:):

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=0.0014680028).

BP6

Variant 5-35670201-G-A is Benign according to our data. Variant chr5-35670201-G-A is described in ClinVar as [Benign]. Clinvar id is 403474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.308 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.1498G>A	p.Asp500Asn	missense_variant	10/37	ENST00000356031.8	NP_079143.3	Q9C093-1A0A140VKD0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPEF2	ENST00000356031.8 linkuse as main transcript	c.1498G>A	p.Asp500Asn	missense_variant	10/37	1	NM_024867.4	ENSP00000348314.3		Q9C093-1

Frequencies

GnomAD3 genomes

AF:

0.0850

AC:

12905

AN:

151856

Hom.:

793

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0970

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.0447

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.0596

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0568

Gnomad OTH

AF:

0.0885

GnomAD3 exomes

AF:

0.100

AC:

24921

AN:

248672

Hom.:

2010

AF XY:

0.0951

AC XY:

12791

AN XY:

134436

show subpopulations

Gnomad AFR exome

AF:

0.0995

Gnomad AMR exome

AF:

0.167

Gnomad ASJ exome

AF:

0.0500

Gnomad EAS exome

AF:

0.329

Gnomad SAS exome

AF:

0.0909

Gnomad FIN exome

AF:

0.0643

Gnomad NFE exome

AF:

0.0581

Gnomad OTH exome

AF:

0.0750

GnomAD4 exome

AF:

0.0743

AC:

108213

AN:

1457148

Hom.:

5977

Cov.:

AF XY:

0.0736

AC XY:

53333

AN XY:

724850

show subpopulations

Gnomad4 AFR exome

AF:

0.100

Gnomad4 AMR exome

AF:

0.162

Gnomad4 ASJ exome

AF:

0.0480

Gnomad4 EAS exome

AF:

0.337

Gnomad4 SAS exome

AF:

0.0888

Gnomad4 FIN exome

AF:

0.0656

Gnomad4 NFE exome

AF:

0.0602

Gnomad4 OTH exome

AF:

0.0826

GnomAD4 genome

AF:

0.0850

AC:

12914

AN:

151974

Hom.:

795

Cov.:

AF XY:

0.0867

AC XY:

6438

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.0970

Gnomad4 AMR

AF:

0.123

Gnomad4 ASJ

AF:

0.0447

Gnomad4 EAS

AF:

0.321

Gnomad4 SAS

AF:

0.101

Gnomad4 FIN

AF:

0.0596

Gnomad4 NFE

AF:

0.0568

Gnomad4 OTH

AF:

0.0866

Alfa

AF:

0.0696

Hom.:

920

Bravo

AF:

0.0924

TwinsUK

AF:

0.0653

AC:

242

ALSPAC

AF:

0.0584

AC:

225

ESP6500AA

AF:

0.0994

AC:

438

ESP6500EA

AF:

0.0528

AC:

454

ExAC

AF:

0.0966

AC:

11729

Asia WGS

AF:

0.180

AC:

626

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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

Uncertain

0.43

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.070

.;.;T;T;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

D;D;D;D;D

MetaRNN

Benign

0.0015

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

2.0

M;.;.;M;M

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.6

D;N;.;N;N

REVEL

Benign

0.17

Sift

Benign

0.26

T;T;.;T;T

Sift4G

Benign

0.40

T;T;.;T;T

Polyphen

1.0

D;D;.;D;.

Vest4

0.11

MPC

0.18

ClinPred

0.014

GERP RS

5.1

Varity_R

0.19

gMVP

0.27

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