Genetic Variant NM_024867.4:c.414+34C>T (chr5-35641717-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024867.4(SPEF2):c.414+34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00856 in 1,584,410 control chromosomes in the GnomAD database, including 323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0086 ( 33 hom., cov: 32)

Exomes 𝑓: 0.0086 ( 290 hom. )

Consequence

SPEF2
NM_024867.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.387

Publications

2 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 5-35641717-C-T is Benign according to our data. Variant chr5-35641717-C-T is described in ClinVar as Benign. ClinVar VariationId is 1181542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0944 is higher than 0.05.

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.414+34C>T		intron	N/A	NP_079143.3
	SPEF2	NM_144722.4		c.414+34C>T		intron	N/A	NP_653323.1	Q9C093-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPEF2	ENST00000356031.8	TSL:1 MANE Select	c.414+34C>T	intron	N/A	ENSP00000348314.3	Q9C093-1
SPEF2	ENST00000509059.5	TSL:1	c.414+34C>T	intron	N/A	ENSP00000421593.1	D6REZ4
SPEF2	ENST00000282469.10	TSL:1	c.414+34C>T	intron	N/A	ENSP00000282469.6	Q9C093-3

Frequencies

GnomAD3 genomes

AF:

0.00862

AC:

1311

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00930

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.0259

Gnomad FIN

AF:

0.0125

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00481

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.0175

AC:

3979

AN:

226902

AF XY:

0.0177

show subpopulations

Gnomad AFR exome

AF:

0.00139

Gnomad AMR exome

AF:

0.0184

Gnomad ASJ exome

AF:

0.00205

Gnomad EAS exome

AF:

0.0969

Gnomad FIN exome

AF:

0.0116

Gnomad NFE exome

AF:

0.00556

Gnomad OTH exome

AF:

0.00915

GnomAD4 exome

AF:

0.00856

AC:

12255

AN:

1432212

Hom.:

290

Cov.:

AF XY:

0.00922

AC XY:

6555

AN XY:

710900

show subpopulations

African (AFR)

AF:

0.000782

AC:

AN:

31986

American (AMR)

AF:

0.0187

AC:

737

AN:

39450

Ashkenazi Jewish (ASJ)

AF:

0.00142

AC:

AN:

24610

East Asian (EAS)

AF:

0.0916

AC:

3616

AN:

39484

South Asian (SAS)

AF:

0.0329

AC:

2639

AN:

80308

European-Finnish (FIN)

AF:

0.0111

AC:

585

AN:

52492

Middle Eastern (MID)

AF:

0.00978

AC:

AN:

4702

European-Non Finnish (NFE)

AF:

0.00364

AC:

4001

AN:

1100188

Other (OTH)

AF:

0.00968

AC:

571

AN:

58992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

572

1145

1717

2290

2862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

202

404

606

808

1010

<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:

0.00859

AC:

1308

AN:

152198

Hom.:

Cov.:

AF XY:

0.00992

AC XY:

738

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

41534

American (AMR)

AF:

0.00928

AC:

142

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.102

AC:

526

AN:

5180

South Asian (SAS)

AF:

0.0253

AC:

122

AN:

4820

European-Finnish (FIN)

AF:

0.0125

AC:

132

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00481

AC:

327

AN:

67994

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

139

209

278

348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00754

Hom.:

Bravo

AF:

0.00787

Asia WGS

AF:

0.0450

AC:

155

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.9

(source)

DANN

Benign

0.34

PhyloP100

-0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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