Variant 5-35654609-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024867.4(SPEF2):c.861C>T(p.Asp287Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 1,612,478 control chromosomes in the GnomAD database, including 265,181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 27652 hom., cov: 32)

Exomes 𝑓: 0.57 ( 237529 hom. )

Consequence

SPEF2
NM_024867.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.121

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 5-35654609-C-T is Benign according to our data. Variant chr5-35654609-C-T is described in ClinVar as [Benign]. Clinvar id is 403473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.121 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 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.861C>T	p.Asp287Asp	synonymous_variant	7/37	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.861C>T	p.Asp287Asp	synonymous_variant	7/37	1	NM_024867.4	ENSP00000348314.3		Q9C093-1

Frequencies

GnomAD3 genomes

AF:

0.597

AC:

90607

AN:

151856

Hom.:

27610

Cov.:

show subpopulations

Gnomad AFR

AF:

0.682

Gnomad AMI

AF:

0.480

Gnomad AMR

AF:

0.646

Gnomad ASJ

AF:

0.573

Gnomad EAS

AF:

0.738

Gnomad SAS

AF:

0.675

Gnomad FIN

AF:

0.470

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.541

Gnomad OTH

AF:

0.585

GnomAD3 exomes

AF:

0.603

AC:

151091

AN:

250526

Hom.:

46749

AF XY:

0.596

AC XY:

80701

AN XY:

135494

show subpopulations

Gnomad AFR exome

AF:

0.689

Gnomad AMR exome

AF:

0.741

Gnomad ASJ exome

AF:

0.565

Gnomad EAS exome

AF:

0.738

Gnomad SAS exome

AF:

0.659

Gnomad FIN exome

AF:

0.490

Gnomad NFE exome

AF:

0.539

Gnomad OTH exome

AF:

0.572

GnomAD4 exome

AF:

0.567

AC:

827403

AN:

1460506

Hom.:

237529

Cov.:

AF XY:

0.567

AC XY:

412259

AN XY:

726540

show subpopulations

Gnomad4 AFR exome

AF:

0.688

Gnomad4 AMR exome

AF:

0.726

Gnomad4 ASJ exome

AF:

0.565

Gnomad4 EAS exome

AF:

0.763

Gnomad4 SAS exome

AF:

0.658

Gnomad4 FIN exome

AF:

0.497

Gnomad4 NFE exome

AF:

0.545

Gnomad4 OTH exome

AF:

0.582

GnomAD4 genome

AF:

0.597

AC:

90712

AN:

151972

Hom.:

27652

Cov.:

AF XY:

0.596

AC XY:

44244

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.682

Gnomad4 AMR

AF:

0.647

Gnomad4 ASJ

AF:

0.573

Gnomad4 EAS

AF:

0.737

Gnomad4 SAS

AF:

0.676

Gnomad4 FIN

AF:

0.470

Gnomad4 NFE

AF:

0.541

Gnomad4 OTH

AF:

0.583

Alfa

AF:

0.556

Hom.:

29998

Bravo

AF:

0.613

Asia WGS

AF:

0.679

AC:

2361

AN:

3478

EpiCase

AF:

0.539

EpiControl

AF:

0.524

ClinVar

Significance: Benign

Submissions summary: Benign:4

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 04, 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 -

Spermatogenic failure 43

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.8

DANN

Benign

0.45

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