rs78576797

chr5-35695742-T-Cchr5-35695742-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_024867.4(SPEF2):c.1983T>C(p.Asn661=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0227 in 1,609,400 control chromosomes in the GnomAD database, including 706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (69 hom., cov: 32)
  • Exomes 𝑓: 0.023 (637 hom.)
• Consequence: SPEF2 NM_024867.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.860

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-35695742-T-C is Benign according to our data. Variant chr5-35695742-T-C is described in ClinVar as [Benign]. Clinvar id is 403476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.86 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPEF2	NM_024867.4	c.1983T>C	p.Asn661=	synonymous_variant	14/37	ENST00000356031.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPEF2	ENST00000356031.8	c.1983T>C	p.Asn661=	synonymous_variant	14/37	1	NM_024867.4	P2
	ENST00000510433.1	n.251+2216A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0217 AC: 3309 AN: 152206 Hom.: 68 Cov.: 32

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0181

Gnomad ASJ AF: 0.0762

Gnomad EAS AF: 0.00462

Gnomad SAS AF: 0.0544

Gnomad FIN AF: 0.0312

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0258

GnomAD3 exomes AF: 0.0271 AC: 6586 AN: 243186 Hom.: 147 AF XY: 0.0297 AC XY: 3911 AN XY: 131824

Gnomad AFR exome AF: 0.0128

Gnomad AMR exome AF: 0.0125

Gnomad ASJ exome AF: 0.0849

Gnomad EAS exome AF: 0.00496

Gnomad SAS exome AF: 0.0581

Gnomad FIN exome AF: 0.0323

Gnomad NFE exome AF: 0.0221

Gnomad OTH exome AF: 0.0347

GnomAD4 exome AF: 0.0228 AC: 33235 AN: 1457076 Hom.: 637 Cov.: 29 AF XY: 0.0245 AC XY: 17744 AN XY: 724486

Gnomad4 AFR exome AF: 0.0132

Gnomad4 AMR exome AF: 0.0130

Gnomad4 ASJ exome AF: 0.0848

Gnomad4 EAS exome AF: 0.00296

Gnomad4 SAS exome AF: 0.0611

Gnomad4 FIN exome AF: 0.0322

Gnomad4 NFE exome AF: 0.0187

Gnomad4 OTH exome AF: 0.0289

GnomAD4 genome AF: 0.0218 AC: 3319 AN: 152324 Hom.: 69 Cov.: 32 AF XY: 0.0230 AC XY: 1712 AN XY: 74486

Gnomad4 AFR AF: 0.0141

Gnomad4 AMR AF: 0.0181

Gnomad4 ASJ AF: 0.0762

Gnomad4 EAS AF: 0.00463

Gnomad4 SAS AF: 0.0549

Gnomad4 FIN AF: 0.0312

Gnomad4 NFE AF: 0.0220

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0230 Hom.: 39

Bravo AF: 0.0201

Asia WGS AF: 0.0360 AC: 126 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	-0.90
Cadd	Benign	0.23
Dann	Benign	0.57

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: rs78576797; hg19: chr5-35695844;