chr5-35641717-C-T

Variant names:

• chr5-35641717-C-T
• rs2131988
• NM_024867.4:c.414+34C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.387
• 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 Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1181542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0944 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.414+34C>T		intron	N/A	NP_079143.3
	SPEF2	NM_144722.4		c.414+34C>T		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.414+34C>T		intron	N/A	ENSP00000348314.3	Q9C093-1
	SPEF2	ENST00000509059.5	TSL:1	c.414+34C>T		intron	N/A	ENSP00000421593.1	D6REZ4
	SPEF2	ENST00000282469.10	TSL:1	c.414+34C>T		intron	N/A	ENSP00000282469.6	Q9C093-3

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

GnomAD2 exomes AF: 0.0175 AC: 3979 AN: 226902 AF XY: 0.0177

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 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

African (AFR) AF: 0.000782 AC: 25 AN: 31986

American (AMR) AF: 0.0187 AC: 737 AN: 39450

Ashkenazi Jewish (ASJ) AF: 0.00142 AC: 35 AN: 24610

East Asian (EAS) AF: 0.0916 AC: 3616 AN: 39484

South Asian (SAS) AF: 0.0329 AC: 2639 AN: 80308

European-Finnish (FIN) AF: 0.0111 AC: 585 AN: 52492

Middle Eastern (MID) AF: 0.00978 AC: 46 AN: 4702

European-Non Finnish (NFE) AF: 0.00364 AC: 4001 AN: 1100188

Other (OTH) AF: 0.00968 AC: 571 AN: 58992

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

African (AFR) AF: 0.00108 AC: 45 AN: 41534

American (AMR) AF: 0.00928 AC: 142 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.102 AC: 526 AN: 5180

South Asian (SAS) AF: 0.0253 AC: 122 AN: 4820

European-Finnish (FIN) AF: 0.0125 AC: 132 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00481 AC: 327 AN: 67994

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00754 Hom.: 16

Bravo AF: 0.00787

Asia WGS AF: 0.0450 AC: 155 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.34
PhyloP100		-0.39
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: rs2131988; hg19: chr5-35641819; COSMIC: COSV56800828; COSMIC: COSV56800828;