Variant rs6451206 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.2142T>C(p.Asn714Asn) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 1,606,028 control chromosomes in the GnomAD database, including 232,276 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 22330 hom., cov: 32)

Exomes 𝑓: 0.53 ( 209946 hom. )

Consequence

SPEF2
NM_024867.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0002073

Clinical Significance

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

Conservation

PhyloP100: -0.252

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=-0.83).

BP6

Variant 5-35700496-T-C is Benign according to our data. Variant chr5-35700496-T-C is described in ClinVar as [Benign]. Clinvar id is 403477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.252 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.555 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.2142T>C	p.Asn714Asn	splice_region_variant, synonymous_variant	16/37	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.2142T>C	p.Asn714Asn	splice_region_variant, synonymous_variant	16/37	1	NM_024867.4	ENSP00000348314.3		Q9C093-1

Frequencies

GnomAD3 genomes

AF:

0.537

AC:

81529

AN:

151906

Hom.:

22309

Cov.:

show subpopulations

Gnomad AFR

AF:

0.561

Gnomad AMI

AF:

0.559

Gnomad AMR

AF:

0.453

Gnomad ASJ

AF:

0.562

Gnomad EAS

AF:

0.261

Gnomad SAS

AF:

0.433

Gnomad FIN

AF:

0.620

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.555

Gnomad OTH

AF:

0.529

GnomAD3 exomes

AF:

0.500

AC:

122676

AN:

245228

Hom.:

32299

AF XY:

0.505

AC XY:

67354

AN XY:

133262

show subpopulations

Gnomad AFR exome

AF:

0.560

Gnomad AMR exome

AF:

0.353

Gnomad ASJ exome

AF:

0.578

Gnomad EAS exome

AF:

0.263

Gnomad SAS exome

AF:

0.451

Gnomad FIN exome

AF:

0.599

Gnomad NFE exome

AF:

0.561

Gnomad OTH exome

AF:

0.537

GnomAD4 exome

AF:

0.532

AC:

774160

AN:

1454004

Hom.:

209946

Cov.:

AF XY:

0.532

AC XY:

384302

AN XY:

722936

show subpopulations

Gnomad4 AFR exome

AF:

0.566

Gnomad4 AMR exome

AF:

0.368

Gnomad4 ASJ exome

AF:

0.575

Gnomad4 EAS exome

AF:

0.239

Gnomad4 SAS exome

AF:

0.454

Gnomad4 FIN exome

AF:

0.593

Gnomad4 NFE exome

AF:

0.551

Gnomad4 OTH exome

AF:

0.523

GnomAD4 genome

AF:

0.537

AC:

81597

AN:

152024

Hom.:

22330

Cov.:

AF XY:

0.536

AC XY:

39858

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.561

Gnomad4 AMR

AF:

0.452

Gnomad4 ASJ

AF:

0.562

Gnomad4 EAS

AF:

0.262

Gnomad4 SAS

AF:

0.433

Gnomad4 FIN

AF:

0.620

Gnomad4 NFE

AF:

0.555

Gnomad4 OTH

AF:

0.532

Alfa

AF:

0.545

Hom.:

48126

Bravo

AF:

0.525

Asia WGS

AF:

0.402

AC:

1400

AN:

3478

EpiCase

AF:

0.561

EpiControl

AF:

0.569

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

-0.83

CADD

Benign

1.0

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00021

dbscSNV1_RF

Benign

0.020

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