rs7731139

Variant names:

• chr5-35727887-A-G
• rs7731139
• NM_024867.4:c.3063+64A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024867.4(SPEF2):​c.3063+64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00611 in 1,545,690 control chromosomes in the GnomAD database, including 558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (322 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (236 hom.)
• Consequence: SPEF2 NM_024867.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.565
• Publications: 0 publications found

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):

• spermatogenic failure 43

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000248969 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-35727887-A-G is Benign according to our data. Variant chr5-35727887-A-G is described in ClinVar as [Benign]. Clinvar id is 1245534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPEF2	NM_024867.4	c.3063+64A>G		intron_variant	Intron 21 of 36	ENST00000356031.8	NP_079143.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPEF2	ENST00000356031.8	c.3063+64A>G		intron_variant	Intron 21 of 36	1	NM_024867.4	ENSP00000348314.3

Frequencies

GnomAD3 genomes AF: 0.0330 AC: 5025 AN: 152134 Hom.: 321 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00792

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0234

GnomAD4 exome AF: 0.00316 AC: 4407 AN: 1393438 Hom.: 236 AF XY: 0.00276 AC XY: 1904 AN XY: 690694

African (AFR) AF: 0.118 AC: 3689 AN: 31238

American (AMR) AF: 0.00500 AC: 184 AN: 36826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23080

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38696

South Asian (SAS) AF: 0.000381 AC: 29 AN: 76016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50520

Middle Eastern (MID) AF: 0.00273 AC: 15 AN: 5496

European-Non Finnish (NFE) AF: 0.0000791 AC: 85 AN: 1073944

Other (OTH) AF: 0.00701 AC: 404 AN: 57622

GnomAD4 genome AF: 0.0331 AC: 5042 AN: 152252 Hom.: 322 Cov.: 32 AF XY: 0.0315 AC XY: 2343 AN XY: 74440

African (AFR) AF: 0.117 AC: 4856 AN: 41518

American (AMR) AF: 0.00791 AC: 121 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68028

Other (OTH) AF: 0.0232 AC: 49 AN: 2114

Alfa AF: 0.0369 Hom.: 48

Bravo AF: 0.0373

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 01, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.29
DANN	Benign	0.35
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7731139; hg19: chr5-35727989;