rs1056801

Positions:

• chr2-241352892-T-C

Variant summary

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

The NM_004404.5(SEPTIN2):​c.*955T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,306 control chromosomes in the GnomAD database, including 1,192 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 0.11 (1192 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SEPTIN2 NM_004404.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN2	NM_004404.5	c.*955T>C		3_prime_UTR_variant	13/13	ENST00000391971.7	NP_004395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEPTIN2	ENST00000391971.7	c.*955T>C		3_prime_UTR_variant	13/13	1	NM_004404.5	ENSP00000375832	P1
	ENST00000414896.1	n.66+147A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16821 AN: 152188 Hom.: 1193 Cov.: 33

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.129

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.110 AC: 16814 AN: 152306 Hom.: 1192 Cov.: 33 AF XY: 0.108 AC XY: 8056 AN XY: 74488

Gnomad4 AFR AF: 0.0312

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.129

Alfa AF: 0.132 Hom.: 545

Bravo AF: 0.106

Asia WGS AF: 0.0980 AC: 342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1056801; hg19: chr2-242292307; COSMIC: COSV50884334; COSMIC: COSV50884334;