2-213396532-A-G

Position:

• chr2-213396532-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024532.5(SPAG16):​c.942+21413A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0647 in 316,166 control chromosomes in the GnomAD database, including 2,242 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 0.099 (1947 hom., cov: 32)
  • Exomes 𝑓: 0.033 (295 hom.)
• Consequence: SPAG16 NM_024532.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165

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]

SPAG16 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPAG16	NM_024532.5	c.942+21413A>G		intron_variant		ENST00000331683.10	NP_078808.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPAG16	ENST00000331683.10	c.942+21413A>G		intron_variant		1	NM_024532.5	ENSP00000332592.5
SPAG16	ENST00000447990.1	c.942+21413A>G		intron_variant		1		ENSP00000400847.1
SPAG16	ENST00000406979.6	n.*943+21413A>G		intron_variant		1		ENSP00000385496.2
SPAG16	ENST00000452556.5	n.*508+21413A>G		intron_variant		2		ENSP00000398926.1

Frequencies

GnomAD3 genomes AF: 0.0987 AC: 15020 AN: 152112 Hom.: 1937 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0487

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0373

Gnomad FIN AF: 0.0160

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0180

Gnomad OTH AF: 0.0819

GnomAD4 exome AF: 0.0330 AC: 5404 AN: 163938 Hom.: 295 AF XY: 0.0329 AC XY: 3064 AN XY: 93052

Gnomad4 AFR exome AF: 0.306

Gnomad4 AMR exome AF: 0.0269

Gnomad4 ASJ exome AF: 0.0659

Gnomad4 EAS exome AF: 0.00120

Gnomad4 SAS exome AF: 0.0412

Gnomad4 FIN exome AF: 0.0144

Gnomad4 NFE exome AF: 0.0176

Gnomad4 OTH exome AF: 0.0409

GnomAD4 genome AF: 0.0990 AC: 15064 AN: 152228 Hom.: 1947 Cov.: 32 AF XY: 0.0956 AC XY: 7116 AN XY: 74440

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.0485

Gnomad4 ASJ AF: 0.0608

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0373

Gnomad4 FIN AF: 0.0160

Gnomad4 NFE AF: 0.0180

Gnomad4 OTH AF: 0.0810

Alfa AF: 0.0686 Hom.: 165

Bravo AF: 0.111

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.78

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: rs16850268; hg19: chr2-214261256;