rs13170082

Positions:

• chr5-35708993-C-G
• chr5-35708993-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024867.4(SPEF2):​c.2711C>G​(p.Ala904Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A904V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: SPEF2 NM_024867.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053021103).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPEF2	NM_024867.4	c.2711C>G	p.Ala904Gly	missense_variant	19/37	ENST00000356031.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPEF2	ENST00000356031.8	c.2711C>G	p.Ala904Gly	missense_variant	19/37	1	NM_024867.4	P2
	ENST00000510433.1	n.174-10958G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Benign	0.016	.;T;T;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.71	T;T;T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.053	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.7	.;.;L;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.96	N;.;N;N
REVEL	Benign	0.12
Sift	Benign	0.30	T;.;T;T
Sift4G	Benign	0.16	T;.;T;T
Polyphen		0.0010	B;.;B;B
Vest4		0.084
MutPred		0.060		.;Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);.;
MVP		0.12
MPC		0.038
ClinPred		0.053	T
GERP RS		-2.8
Varity_R		0.059
gMVP		0.21

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: rs13170082; hg19: chr5-35709095;