5-35641546-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_024867.4(SPEF2):c.277G>A(p.Ala93Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000533 in 1,613,772 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00063 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 1 hom. )

Consequence

SPEF2
NM_024867.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 8.58

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia
Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
spermatogenic failure 43
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
non-syndromic male infertility due to sperm motility disorder
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SPEF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012461096).

BP6

Variant 5-35641546-G-A is Benign according to our data. Variant chr5-35641546-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3036780.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000631 (96/152190) while in subpopulation EAS AF = 0.00213 (11/5168). AF 95% confidence interval is 0.00119. There are 0 homozygotes in GnomAd4. There are 59 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024867.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPEF2	NM_024867.4	MANE Select	c.277G>A	p.Ala93Thr	missense	Exon 3 of 37	NP_079143.3
	SPEF2	NM_144722.4		c.277G>A	p.Ala93Thr	missense	Exon 3 of 10	NP_653323.1	Q9C093-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPEF2	ENST00000356031.8	TSL:1 MANE Select	c.277G>A	p.Ala93Thr	missense	Exon 3 of 37	ENSP00000348314.3	Q9C093-1
SPEF2	ENST00000509059.5	TSL:1	c.277G>A	p.Ala93Thr	missense	Exon 3 of 19	ENSP00000421593.1	D6REZ4
SPEF2	ENST00000282469.10	TSL:1	c.277G>A	p.Ala93Thr	missense	Exon 3 of 10	ENSP00000282469.6	Q9C093-3

Frequencies

GnomAD3 genomes

AF:

0.000631

AC:

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00368

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.000768

AC:

193

AN:

251166

AF XY:

0.000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00103

Gnomad FIN exome

AF:

0.00467

Gnomad NFE exome

AF:

0.000502

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000523

AC:

764

AN:

1461582

Hom.:

Cov.:

AF XY:

0.000518

AC XY:

377

AN XY:

727108

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33456

American (AMR)

AF:

0.0000672

AC:

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00179

AC:

AN:

39688

South Asian (SAS)

AF:

0.000162

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00500

AC:

267

AN:

53412

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000327

AC:

364

AN:

1111838

Other (OTH)

AF:

0.000679

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

141

188

235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000631

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.000793

AC XY:

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41534

American (AMR)

AF:

0.000720

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00213

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00368

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000441

AC:

AN:

67998

Other (OTH)

AF:

0.00190

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000447

Hom.:

Bravo

AF:

0.000272

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000914

AC:

111

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

SPEF2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.19

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.91

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.029

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.7

PhyloP100

8.6

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.45

Sift

Uncertain

0.014

Sift4G

Uncertain

0.034

Polyphen

0.99

Vest4

0.71

MVP

0.41

MPC

0.23

ClinPred

0.11

GERP RS

5.9

Varity_R

0.75

gMVP

0.36

Mutation Taster

=53/47

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over