2-214144634-T-C

Variant names:

• chr2-214144634-T-C
• rs7597126
• NM_024532.5:c.1594-4506T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024532.5(SPAG16):​c.1594-4506T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,946 control chromosomes in the GnomAD database, including 13,404 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (13404 hom., cov: 32)
• Consequence: SPAG16 NM_024532.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632
• Publications: 3 publications found

Genes affected

SPAG16 (HGNC:23225): (sperm associated antigen 16) Cilia and flagella are comprised of a microtubular backbone, the axoneme, which is organized by the basal body and surrounded by plasma membrane. SPAG16 encodes 2 major proteins that associate with the axoneme of sperm tail and the nucleus of postmeiotic germ cells, respectively (Zhang et al., 2007 [PubMed 17699735]).[supplied by OMIM, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024532.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG16	NM_024532.5	MANE Select	c.1594-4506T>C		intron	N/A	NP_078808.3
	SPAG16	NR_047659.2		n.1789-4506T>C		intron	N/A
	SPAG16	NR_047660.2		n.1495-4506T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG16	ENST00000331683.10	TSL:1 MANE Select	c.1594-4506T>C		intron	N/A	ENSP00000332592.5
	SPAG16	ENST00000406979.6	TSL:1	n.*1595-4506T>C		intron	N/A	ENSP00000385496.2
	SPAG16	ENST00000451561.1	TSL:3	c.466-4506T>C		intron	N/A	ENSP00000416600.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59249 AN: 151828 Hom.: 13408 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.390 AC: 59249 AN: 151946 Hom.: 13404 Cov.: 32 AF XY: 0.391 AC XY: 29013 AN XY: 74252

African (AFR) AF: 0.161 AC: 6669 AN: 41492

American (AMR) AF: 0.407 AC: 6203 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1586 AN: 3470

East Asian (EAS) AF: 0.205 AC: 1064 AN: 5182

South Asian (SAS) AF: 0.353 AC: 1699 AN: 4818

European-Finnish (FIN) AF: 0.591 AC: 6225 AN: 10532

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.508 AC: 34517 AN: 67908

Other (OTH) AF: 0.394 AC: 830 AN: 2104

Alfa AF: 0.473 Hom.: 13828

Bravo AF: 0.362

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.51
DANN	Benign	0.78
PhyloP100		-0.63
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: rs7597126; hg19: chr2-215009358;