2-214100920-G-C

Variant names:

• chr2-214100920-G-C
• rs6756154
• NM_024532.5:c.1528-7276G>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.1528-7276G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 151,850 control chromosomes in the GnomAD database, including 8,824 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 0.34 (8824 hom., cov: 32)
• Consequence: SPAG16 NM_024532.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129
• Publications: 0 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]

ENSG00000308168 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.345 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.1528-7276G>C		intron	N/A	NP_078808.3
	SPAG16	NR_047659.2		n.1723-7276G>C		intron	N/A
	SPAG16	NR_047660.2		n.1429-7276G>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.1528-7276G>C		intron	N/A	ENSP00000332592.5
	SPAG16	ENST00000406979.6	TSL:1	n.*1529-7276G>C		intron	N/A	ENSP00000385496.2
	SPAG16	ENST00000451561.1	TSL:3	c.400-7276G>C		intron	N/A	ENSP00000416600.1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50902 AN: 151732 Hom.: 8811 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.336 AC: 50950 AN: 151850 Hom.: 8824 Cov.: 32 AF XY: 0.334 AC XY: 24779 AN XY: 74208

African (AFR) AF: 0.350 AC: 14502 AN: 41416

American (AMR) AF: 0.345 AC: 5257 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1070 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1010 AN: 5146

South Asian (SAS) AF: 0.254 AC: 1225 AN: 4818

European-Finnish (FIN) AF: 0.347 AC: 3644 AN: 10514

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23142 AN: 67934

Other (OTH) AF: 0.321 AC: 676 AN: 2108

Alfa AF: 0.344 Hom.: 1170

Bravo AF: 0.337

Asia WGS AF: 0.206 AC: 713 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.41
PhyloP100		0.13
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: rs6756154; hg19: chr2-214965644;