rs12694997

Variant names:

• chr2-241323571-G-A
• rs12694997
• NM_004404.5:c.-17-645G>A

Variant summary

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

The NM_004404.5(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 NM_004404.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 54 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004404.5. 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
	SEPTIN2	NM_004404.5	MANE Select	c.-17-645G>A		intron	N/A	NP_004395.1	Q15019-1
	SEPTIN2	NM_001349287.2		c.175-2422G>A		intron	N/A	NP_001336216.1
	SEPTIN2	NM_001282972.2		c.89-645G>A		intron	N/A	NP_001269901.1	Q15019-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN2	ENST00000391971.7	TSL:1 MANE Select	c.-17-645G>A		intron	N/A	ENSP00000375832.2	Q15019-1
	SEPTIN2	ENST00000401990.5	TSL:1	c.-17-645G>A		intron	N/A	ENSP00000385109.1	Q15019-3
	SEPTIN2	ENST00000360051.7	TSL:1	c.-17-645G>A		intron	N/A	ENSP00000353157.3	Q15019-1

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

African (AFR) AF: 0.135 AC: 5609 AN: 41446

American (AMR) AF: 0.178 AC: 2713 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 993 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5180

South Asian (SAS) AF: 0.0629 AC: 303 AN: 4820

European-Finnish (FIN) AF: 0.210 AC: 2215 AN: 10550

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16069 AN: 67948

Other (OTH) AF: 0.208 AC: 439 AN: 2112

Alfa AF: 0.224 Hom.: 16955

Bravo AF: 0.191

Asia WGS AF: 0.0390 AC: 138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.92
DANN	Benign	0.60
PhyloP100		-1.9
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: rs12694997; hg19: chr2-242262986;