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GeneBe

2-241337694-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_004404.5(SEPTIN2):c.498G>A(p.Ala166=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,613,742 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0028 ( 20 hom. )

Consequence

SEPTIN2
NM_004404.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0830
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-241337694-G-A is Benign according to our data. Variant chr2-241337694-G-A is described in ClinVar as [Benign]. Clinvar id is 708068.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.083 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 5 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEPTIN2NM_004404.5 linkuse as main transcriptc.498G>A p.Ala166= synonymous_variant 7/13 ENST00000391971.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEPTIN2ENST00000391971.7 linkuse as main transcriptc.498G>A p.Ala166= synonymous_variant 7/131 NM_004404.5 P1Q15019-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00284
AC:
432
AN:
152064
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00219
Gnomad AMR
AF:
0.000721
Gnomad ASJ
AF:
0.0190
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00293
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00454
Gnomad OTH
AF:
0.00192
GnomAD3 exomes
AF:
0.00318
AC:
798
AN:
251322
Hom.:
5
AF XY:
0.00328
AC XY:
446
AN XY:
135826
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000347
Gnomad ASJ exome
AF:
0.0189
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000588
Gnomad FIN exome
AF:
0.00333
Gnomad NFE exome
AF:
0.00425
Gnomad OTH exome
AF:
0.00359
GnomAD4 exome
AF:
0.00276
AC:
4039
AN:
1461560
Hom.:
20
Cov.:
30
AF XY:
0.00288
AC XY:
2093
AN XY:
727086
show subpopulations
Gnomad4 AFR exome
AF:
0.000358
Gnomad4 AMR exome
AF:
0.000537
Gnomad4 ASJ exome
AF:
0.0188
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000615
Gnomad4 FIN exome
AF:
0.00433
Gnomad4 NFE exome
AF:
0.00272
Gnomad4 OTH exome
AF:
0.00336
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00284
AC:
432
AN:
152182
Hom.:
1
Cov.:
32
AF XY:
0.00266
AC XY:
198
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.000169
Gnomad4 AMR
AF:
0.000720
Gnomad4 ASJ
AF:
0.0190
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00293
Gnomad4 NFE
AF:
0.00454
Gnomad4 OTH
AF:
0.00190
Alfa
AF:
0.00475
Hom.:
1
Bravo
AF:
0.00221
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00382
EpiControl
AF:
0.00344

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 28, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.34
Cadd
Benign
4.4
Dann
Benign
0.60
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs34185831; hg19: chr2-242277109; COSMIC: COSV63472257; COSMIC: COSV63472257; API