rs115898419

Variant names:

• chr5-35712799-G-A
• rs115898419
• NM_024867.4:c.2840-13G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_024867.4(SPEF2):​c.2840-13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 1,612,932 control chromosomes in the GnomAD database, including 714 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (64 hom., cov: 34)
  • Exomes 𝑓: 0.023 (650 hom.)
• Consequence: SPEF2 NM_024867.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.362
• Publications: 5 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 5-35712799-G-A is Benign according to our data. Variant chr5-35712799-G-A is described in ClinVar as Benign. ClinVar VariationId is 403480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPEF2	NM_024867.4	c.2840-13G>A		intron_variant	Intron 19 of 36	ENST00000356031.8	NP_079143.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPEF2	ENST00000356031.8	c.2840-13G>A		intron_variant	Intron 19 of 36	1	NM_024867.4	ENSP00000348314.3

Frequencies

GnomAD3 genomes AF: 0.0187 AC: 2850 AN: 152120 Hom.: 64 Cov.: 34

Gnomad AFR AF: 0.00302

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0180

Gnomad ASJ AF: 0.0757

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.0535

Gnomad FIN AF: 0.0317

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0221

Gnomad OTH AF: 0.0244

GnomAD2 exomes AF: 0.0271 AC: 6727 AN: 248304 AF XY: 0.0299

Gnomad AFR exome AF: 0.00208

Gnomad AMR exome AF: 0.0130

Gnomad ASJ exome AF: 0.0854

Gnomad EAS exome AF: 0.00490

Gnomad FIN exome AF: 0.0334

Gnomad NFE exome AF: 0.0227

Gnomad OTH exome AF: 0.0361

GnomAD4 exome AF: 0.0228 AC: 33331 AN: 1460694 Hom.: 650 Cov.: 31 AF XY: 0.0246 AC XY: 17852 AN XY: 726606

African (AFR) AF: 0.00380 AC: 127 AN: 33464

American (AMR) AF: 0.0132 AC: 588 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.0853 AC: 2226 AN: 26104

East Asian (EAS) AF: 0.00280 AC: 111 AN: 39660

South Asian (SAS) AF: 0.0618 AC: 5323 AN: 86082

European-Finnish (FIN) AF: 0.0328 AC: 1749 AN: 53252

Middle Eastern (MID) AF: 0.0881 AC: 507 AN: 5754

European-Non Finnish (NFE) AF: 0.0189 AC: 21005 AN: 1111338

Other (OTH) AF: 0.0281 AC: 1695 AN: 60348

GnomAD4 genome AF: 0.0188 AC: 2856 AN: 152238 Hom.: 64 Cov.: 34 AF XY: 0.0202 AC XY: 1502 AN XY: 74444

African (AFR) AF: 0.00303 AC: 126 AN: 41542

American (AMR) AF: 0.0179 AC: 274 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0757 AC: 263 AN: 3472

East Asian (EAS) AF: 0.00444 AC: 23 AN: 5184

South Asian (SAS) AF: 0.0539 AC: 260 AN: 4822

European-Finnish (FIN) AF: 0.0317 AC: 336 AN: 10598

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0221 AC: 1502 AN: 68020

Other (OTH) AF: 0.0255 AC: 54 AN: 2116

Alfa AF: 0.0319 Hom.: 22

Bravo AF: 0.0168

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Benign	0.80
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs115898419; hg19: chr5-35712901;