Genetic Variant NM_004404.5:c.*955T>C (chr2-241352892-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.119

Publications

16 publications found

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]

SEPTIN2 links:

ENSG00000223374 (HGNC:):

ENSG00000223374 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SEPTIN2	NM_004404.5	MANE Select	c.*955T>C	3_prime_UTR	Exon 13 of 13	NP_004395.1
SEPTIN2	NM_001349287.2		c.*955T>C	3_prime_UTR	Exon 14 of 14	NP_001336216.1
SEPTIN2	NM_001282972.2		c.*955T>C	3_prime_UTR	Exon 14 of 14	NP_001269901.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SEPTIN2	ENST00000391971.7	TSL:1 MANE Select	c.*955T>C	3_prime_UTR	Exon 13 of 13	ENSP00000375832.2
SEPTIN2	ENST00000360051.7	TSL:1	c.*955T>C	3_prime_UTR	Exon 14 of 14	ENSP00000353157.3
SEPTIN2	ENST00000391973.6	TSL:1	c.*955T>C	3_prime_UTR	Exon 13 of 13	ENSP00000375834.2

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16821

AN:

152188

Hom.:

1193

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.110

AC:

16814

AN:

152306

Hom.:

1192

Cov.:

AF XY:

0.108

AC XY:

8056

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0312

AC:

1295

AN:

41568

American (AMR)

AF:

0.145

AC:

2219

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

423

AN:

3472

East Asian (EAS)

AF:

0.115

AC:

595

AN:

5190

South Asian (SAS)

AF:

0.101

AC:

487

AN:

4828

European-Finnish (FIN)

AF:

0.119

AC:

1258

AN:

10608

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.150

AC:

10191

AN:

68018

Other (OTH)

AF:

0.129

AC:

273

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

768

1537

2305

3074

3842

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

194

388

582

776

970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.131

Hom.:

783

Bravo

AF:

0.106

Asia WGS

AF:

0.0980

AC:

342

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

0.12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.97

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over