2-213862481-G-T

Variant names:

• chr2-213862481-G-T
• rs2248214
• NM_024532.5:c.1071-4G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024532.5(SPAG16):​c.1071-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00546 in 1,612,676 control chromosomes in the GnomAD database, including 404 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (211 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (193 hom.)
• Consequence: SPAG16 NM_024532.5 splice_region, intron
• Scores: Splicing: ADA: 0.00005070
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.789
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-213862481-G-T is Benign according to our data. Variant chr2-213862481-G-T is described in ClinVar as Benign. ClinVar VariationId is 767850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0935 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG16	NM_024532.5	MANE Select	c.1071-4G>T		splice_region intron	N/A	NP_078808.3
	SPAG16	NR_047659.2		n.1266-4G>T		splice_region intron	N/A
	SPAG16	NR_047660.2		n.972-4G>T		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG16	ENST00000331683.10	TSL:1 MANE Select	c.1071-4G>T		splice_region intron	N/A	ENSP00000332592.5	Q8N0X2-1
	SPAG16	ENST00000406979.6	TSL:1	n.*1072-4G>T		splice_region intron	N/A	ENSP00000385496.2	F8WB32
	SPAG16	ENST00000451561.1	TSL:3	c.129-4G>T		splice_region intron	N/A	ENSP00000416600.1	H0Y811

Frequencies

GnomAD3 genomes AF: 0.0276 AC: 4199 AN: 151912 Hom.: 209 Cov.: 33

Gnomad AFR AF: 0.0960

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00852

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000568

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000662

Gnomad OTH AF: 0.0230

GnomAD2 exomes AF: 0.00766 AC: 1920 AN: 250640 AF XY: 0.00552

Gnomad AFR exome AF: 0.0997

Gnomad AMR exome AF: 0.00516

Gnomad ASJ exome AF: 0.000498

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000694

Gnomad NFE exome AF: 0.000557

Gnomad OTH exome AF: 0.00540

GnomAD4 exome AF: 0.00314 AC: 4589 AN: 1460646 Hom.: 193 Cov.: 31 AF XY: 0.00277 AC XY: 2011 AN XY: 726492

African (AFR) AF: 0.101 AC: 3384 AN: 33456

American (AMR) AF: 0.00548 AC: 245 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.000345 AC: 9 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86180

European-Finnish (FIN) AF: 0.000618 AC: 33 AN: 53386

Middle Eastern (MID) AF: 0.00975 AC: 56 AN: 5744

European-Non Finnish (NFE) AF: 0.000340 AC: 378 AN: 1111106

Other (OTH) AF: 0.00772 AC: 466 AN: 60330

GnomAD4 genome AF: 0.0277 AC: 4211 AN: 152030 Hom.: 211 Cov.: 33 AF XY: 0.0268 AC XY: 1994 AN XY: 74300

African (AFR) AF: 0.0960 AC: 3978 AN: 41440

American (AMR) AF: 0.00851 AC: 130 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.000568 AC: 6 AN: 10556

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000662 AC: 45 AN: 67994

Other (OTH) AF: 0.0227 AC: 48 AN: 2110

Alfa AF: 0.0211 Hom.: 132

Bravo AF: 0.0318

Asia WGS AF: 0.0120 AC: 40 AN: 3478

EpiCase AF: 0.000656

EpiControl AF: 0.000832

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.29
DANN	Benign	0.38
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000051
dbscSNV1_RF	Benign	0.016
SpliceAI score (max)		0.050		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: rs2248214; hg19: chr2-214727205;