Variant rs201730485 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_024867.4(SPEF2):c.2390A>G(p.Asp797Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000782 in 1,613,526 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00082 ( 2 hom. )

Consequence

SPEF2
NM_024867.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.520

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008966774).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000453 (69/152374) while in subpopulation NFE AF= 0.000882 (60/68034). AF 95% confidence interval is 0.000703. There are 0 homozygotes in gnomad4. There are 28 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPEF2	NM_024867.4 linkuse as main transcript	c.2390A>G	p.Asp797Gly	missense_variant	16/37	ENST00000356031.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPEF2	ENST00000356031.8 linkuse as main transcript	c.2390A>G	p.Asp797Gly	missense_variant	16/37	1	NM_024867.4	P2	Q9C093-1
	ENST00000510433.1 linkuse as main transcript	n.174-2709T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000453

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000882

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000442

AC:

110

AN:

248654

Hom.:

AF XY:

0.000526

AC XY:

AN XY:

134942

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000586

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000816

AC:

1192

AN:

1461152

Hom.:

Cov.:

AF XY:

0.000810

AC XY:

589

AN XY:

726810

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00102

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000941

Gnomad4 OTH exome

AF:

0.000646

GnomAD4 genome

AF:

0.000453

AC:

AN:

152374

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74524

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000882

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000690

Hom.:

Bravo

AF:

0.000461

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000272

AC:

ESP6500EA

AF:

0.00123

AC:

ExAC

AF:

0.000472

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.00107

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, 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: Candidate PCD gene, but no second suspicious variant and no information on this variant -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0029

.;T;T;.

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.67

T;T;T;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.0090

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.8

.;.;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

0.65

N;.;N;N

REVEL

Benign

0.077

Sift

Benign

0.66

T;.;T;T

Sift4G

Benign

0.68

T;.;T;T

Polyphen

0.0030

B;.;B;B

Vest4

0.12

MVP

0.19

MPC

0.034

ClinPred

0.015

GERP RS

3.7

Varity_R

0.094

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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