5-35644234-T-G

Variant names:

• chr5-35644234-T-G
• rs2035994
• NM_024867.4:c.415-121T>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.415-121T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 808,450 control chromosomes in the GnomAD database, including 133,198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (27589 hom., cov: 32)
  • Exomes 𝑓: 0.56 (105609 hom.)
• Consequence: SPEF2 NM_024867.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.341
• Publications: 2 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=-0.86).
• BP6: Variant 5-35644234-T-G is Benign according to our data. Variant chr5-35644234-T-G is described in ClinVar as Benign. ClinVar VariationId is 1221024.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 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.415-121T>G		intron	N/A	NP_079143.3
	SPEF2	NM_144722.4		c.415-121T>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.415-121T>G		intron	N/A	ENSP00000348314.3	Q9C093-1
	SPEF2	ENST00000509059.5	TSL:1	c.415-121T>G		intron	N/A	ENSP00000421593.1	D6REZ4
	SPEF2	ENST00000282469.10	TSL:1	c.415-121T>G		intron	N/A	ENSP00000282469.6	Q9C093-3

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90474 AN: 151790 Hom.: 27547 Cov.: 32

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.542

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.584

GnomAD4 exome AF: 0.561 AC: 368194 AN: 656542 Hom.: 105609 AF XY: 0.563 AC XY: 185026 AN XY: 328782

African (AFR) AF: 0.684 AC: 10476 AN: 15314

American (AMR) AF: 0.679 AC: 8903 AN: 13114

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 7460 AN: 13210

East Asian (EAS) AF: 0.771 AC: 22465 AN: 29132

South Asian (SAS) AF: 0.656 AC: 19954 AN: 30408

European-Finnish (FIN) AF: 0.494 AC: 19558 AN: 39622

Middle Eastern (MID) AF: 0.548 AC: 1244 AN: 2270

European-Non Finnish (NFE) AF: 0.539 AC: 260250 AN: 482440

Other (OTH) AF: 0.576 AC: 17884 AN: 31032

GnomAD4 genome AF: 0.596 AC: 90580 AN: 151908 Hom.: 27589 Cov.: 32 AF XY: 0.595 AC XY: 44189 AN XY: 74244

African (AFR) AF: 0.680 AC: 28157 AN: 41434

American (AMR) AF: 0.647 AC: 9865 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1987 AN: 3470

East Asian (EAS) AF: 0.737 AC: 3806 AN: 5162

South Asian (SAS) AF: 0.675 AC: 3249 AN: 4812

European-Finnish (FIN) AF: 0.471 AC: 4954 AN: 10528

Middle Eastern (MID) AF: 0.545 AC: 158 AN: 290

European-Non Finnish (NFE) AF: 0.541 AC: 36740 AN: 67946

Other (OTH) AF: 0.582 AC: 1228 AN: 2110

Alfa AF: 0.429 Hom.: 1185

Bravo AF: 0.613

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	-0.86
CADD	Benign	5.4
DANN	Benign	0.71
PhyloP100		-0.34
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: rs2035994; hg19: chr5-35644336;