rs115898419

chr5-35712799-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_024867.4(SPEF2):c.2840-13G>A variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.362

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
SPEF2	NM_024867.4	c.2840-13G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000356031.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPEF2	ENST00000356031.8	c.2840-13G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_024867.4	P2
	ENST00000510433.1	n.174-14764C>T		intron_variant, non_coding_transcript_variant		4
SPEF2	ENST00000440995.6	c.2825-13G>A		splice_polypyrimidine_tract_variant, intron_variant		5		A2
SPEF2	ENST00000637569.1	c.2840-13G>A		splice_polypyrimidine_tract_variant, intron_variant		5		A2

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

GnomAD3 exomes AF: 0.0271 AC: 6727 AN: 248304 Hom.: 158 AF XY: 0.0299 AC XY: 4034 AN XY: 134730

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 SAS exome AF: 0.0596

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

Gnomad4 AFR exome AF: 0.00380

Gnomad4 AMR exome AF: 0.0132

Gnomad4 ASJ exome AF: 0.0853

Gnomad4 EAS exome AF: 0.00280

Gnomad4 SAS exome AF: 0.0618

Gnomad4 FIN exome AF: 0.0328

Gnomad4 NFE exome AF: 0.0189

Gnomad4 OTH exome AF: 0.0281

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

Gnomad4 AFR AF: 0.00303

Gnomad4 AMR AF: 0.0179

Gnomad4 ASJ AF: 0.0757

Gnomad4 EAS AF: 0.00444

Gnomad4 SAS AF: 0.0539

Gnomad4 FIN AF: 0.0317

Gnomad4 NFE AF: 0.0221

Gnomad4 OTH AF: 0.0255

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, 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: Frequency -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
Cadd	Benign	18
Dann	Benign	0.80

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

LitVar

Other links and lift over

dbSNP: rs115898419; hg19: chr5-35712901;