2-214108287-G-A

Variant names:

• chr2-214108287-G-A
• rs16851495
• NM_024532.5:c.1593+26G>A

Variant summary

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

The NM_024532.5(SPAG16):​c.1593+26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0755 in 1,551,664 control chromosomes in the GnomAD database, including 5,883 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 0.088 (765 hom., cov: 32)
  • Exomes 𝑓: 0.074 (5118 hom.)
• Consequence: SPAG16 NM_024532.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.52
• Publications: 6 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 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.1593+26G>A		intron	N/A	NP_078808.3
	SPAG16	NR_047659.2		n.1788+26G>A		intron	N/A
	SPAG16	NR_047660.2		n.1494+26G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG16	ENST00000331683.10	TSL:1 MANE Select	c.1593+26G>A		intron	N/A	ENSP00000332592.5
	SPAG16	ENST00000406979.6	TSL:1	n.*1594+26G>A		intron	N/A	ENSP00000385496.2
	SPAG16	ENST00000451561.1	TSL:3	c.465+26G>A		intron	N/A	ENSP00000416600.1

Frequencies

GnomAD3 genomes AF: 0.0876 AC: 13306 AN: 151906 Hom.: 764 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.0706

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.0884

Gnomad FIN AF: 0.0655

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0644

Gnomad OTH AF: 0.0934

GnomAD2 exomes AF: 0.0892 AC: 21361 AN: 239522 AF XY: 0.0870

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.0729

Gnomad ASJ exome AF: 0.0875

Gnomad EAS exome AF: 0.277

Gnomad FIN exome AF: 0.0784

Gnomad NFE exome AF: 0.0653

Gnomad OTH exome AF: 0.0855

GnomAD4 exome AF: 0.0742 AC: 103870 AN: 1399640 Hom.: 5118 Cov.: 23 AF XY: 0.0743 AC XY: 51676 AN XY: 695934

African (AFR) AF: 0.116 AC: 3701 AN: 31822

American (AMR) AF: 0.0730 AC: 3027 AN: 41490

Ashkenazi Jewish (ASJ) AF: 0.0854 AC: 2138 AN: 25044

East Asian (EAS) AF: 0.300 AC: 11709 AN: 39076

South Asian (SAS) AF: 0.0790 AC: 6472 AN: 81954

European-Finnish (FIN) AF: 0.0756 AC: 3998 AN: 52854

Middle Eastern (MID) AF: 0.0953 AC: 534 AN: 5606

European-Non Finnish (NFE) AF: 0.0632 AC: 67202 AN: 1063680

Other (OTH) AF: 0.0876 AC: 5089 AN: 58114

GnomAD4 genome AF: 0.0876 AC: 13316 AN: 152024 Hom.: 765 Cov.: 32 AF XY: 0.0884 AC XY: 6566 AN XY: 74294

African (AFR) AF: 0.115 AC: 4753 AN: 41488

American (AMR) AF: 0.0705 AC: 1075 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 272 AN: 3470

East Asian (EAS) AF: 0.286 AC: 1475 AN: 5166

South Asian (SAS) AF: 0.0879 AC: 423 AN: 4814

European-Finnish (FIN) AF: 0.0655 AC: 692 AN: 10564

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0644 AC: 4379 AN: 67960

Other (OTH) AF: 0.0934 AC: 197 AN: 2110

Alfa AF: 0.0732 Hom.: 111

Bravo AF: 0.0918

Asia WGS AF: 0.181 AC: 628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.018
DANN	Benign	0.59
PhyloP100		-3.5
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: rs16851495; hg19: chr2-214973011; COSMIC: COSV59095599;