rs430828

Variant names:

• chr5-35628718-A-G
• rs430828
• NM_024867.4:c.161+156A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024867.4(SPEF2):​c.161+156A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 151,990 control chromosomes in the GnomAD database, including 2,332 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (2332 hom., cov: 32)
• Consequence: SPEF2 NM_024867.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.652
• 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):

• primary ciliary dyskinesia

  Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• spermatogenic failure 43

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 5-35628718-A-G is Benign according to our data. Variant chr5-35628718-A-G is described in ClinVar as Benign. ClinVar VariationId is 1282434.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024867.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPEF2	NM_024867.4	MANE Select	c.161+156A>G		intron	N/A	NP_079143.3
	SPEF2	NM_144722.4		c.161+156A>G		intron	N/A	NP_653323.1	Q9C093-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPEF2	ENST00000356031.8	TSL:1 MANE Select	c.161+156A>G		intron	N/A	ENSP00000348314.3	Q9C093-1
	SPEF2	ENST00000509059.5	TSL:1	c.161+156A>G		intron	N/A	ENSP00000421593.1	D6REZ4
	SPEF2	ENST00000282469.10	TSL:1	c.161+156A>G		intron	N/A	ENSP00000282469.6	Q9C093-3

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17777 AN: 151872 Hom.: 2318 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0564

Gnomad ASJ AF: 0.0286

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.0592

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0355

Gnomad OTH AF: 0.0910

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.117 AC: 17849 AN: 151990 Hom.: 2332 Cov.: 32 AF XY: 0.114 AC XY: 8496 AN XY: 74306

African (AFR) AF: 0.326 AC: 13473 AN: 41366

American (AMR) AF: 0.0563 AC: 860 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0286 AC: 99 AN: 3464

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5176

South Asian (SAS) AF: 0.0307 AC: 148 AN: 4814

European-Finnish (FIN) AF: 0.0592 AC: 626 AN: 10582

Middle Eastern (MID) AF: 0.0582 AC: 17 AN: 292

European-Non Finnish (NFE) AF: 0.0355 AC: 2417 AN: 68006

Other (OTH) AF: 0.0938 AC: 198 AN: 2110

Alfa AF: 0.0841 Hom.: 171

Bravo AF: 0.127

Asia WGS AF: 0.0520 AC: 179 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.44
PhyloP100		-0.65
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: rs430828; hg19: chr5-35628820;