5-35641717-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.387

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1181542.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPEF2	NM_024867.4	c.414+34C>T		intron_variant		ENST00000356031.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPEF2	ENST00000356031.8	c.414+34C>T		intron_variant		1	NM_024867.4	P2

Frequencies

GnomAD3 genomes AF: 0.00862 AC: 1311 AN: 152080 Hom.: 34 Cov.: 32

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

GnomAD3 exomes AF: 0.0175 AC: 3979 AN: 226902 Hom.: 118 AF XY: 0.0177 AC XY: 2171 AN XY: 122974

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 SAS exome AF: 0.0331

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.: 30 AF XY: 0.00922 AC XY: 6555 AN XY: 710900

Gnomad4 AFR exome AF: 0.000782

Gnomad4 AMR exome AF: 0.0187

Gnomad4 ASJ exome AF: 0.00142

Gnomad4 EAS exome AF: 0.0916

Gnomad4 SAS exome AF: 0.0329

Gnomad4 FIN exome AF: 0.0111

Gnomad4 NFE exome AF: 0.00364

Gnomad4 OTH exome AF: 0.00968

GnomAD4 genome AF: 0.00859 AC: 1308 AN: 152198 Hom.: 33 Cov.: 32 AF XY: 0.00992 AC XY: 738 AN XY: 74412

Gnomad4 AFR AF: 0.00108

Gnomad4 AMR AF: 0.00928

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.0253

Gnomad4 FIN AF: 0.0125

Gnomad4 NFE AF: 0.00481

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00754 Hom.: 16

Bravo AF: 0.00787

Asia WGS AF: 0.0450 AC: 155 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 26, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.9
Dann	Benign	0.34

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: rs2131988; hg19: chr5-35641819; COSMIC: COSV56800828; COSMIC: COSV56800828;