rs12694997

Positions:

• chr2-241323571-G-A

Variant summary

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

The ENST00000391971.7(SEPTIN2):​c.-17-645G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,000 control chromosomes in the GnomAD database, including 3,106 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 0.19 (3106 hom., cov: 32)
• Consequence: SEPTIN2 ENST00000391971.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

Genes affected

SEPTIN2 (HGNC:7729): (septin 2) Enables identical protein binding activity. Predicted to be involved in several processes, including cilium assembly; regulation of exocytosis; and smoothened signaling pathway. Predicted to act upstream of or within regulation of L-glutamate import across plasma membrane and regulation of protein localization. Located in several cellular components, including cytoskeleton; photoreceptor connecting cilium; and sperm annulus. Part of septin complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN2	NM_004404.5	c.-17-645G>A		intron_variant		ENST00000391971.7	NP_004395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEPTIN2	ENST00000391971.7	c.-17-645G>A		intron_variant		1	NM_004404.5	ENSP00000375832	P1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28966 AN: 151880 Hom.: 3108 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0636

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.191 AC: 28960 AN: 152000 Hom.: 3106 Cov.: 32 AF XY: 0.189 AC XY: 14051 AN XY: 74304

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0629

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.208

Alfa AF: 0.232 Hom.: 8947

Bravo AF: 0.191

Asia WGS AF: 0.0390 AC: 138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.92
DANN	Benign	0.60

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: rs12694997; hg19: chr2-242262986;