Genetic Variant SOX2:c.-11A>C (chr3-181712350-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_003106.4(SOX2):c.-11A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000236 in 1,270,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

SOX2
NM_003106.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.08

Publications

0 publications found

Variant links:

Genes affected

SOX2 (HGNC:11195): (SRY-box transcription factor 2) This intronless gene encodes a member of the SRY-related HMG-box (SOX) family of transcription factors involved in the regulation of embryonic development and in the determination of cell fate. The product of this gene is required for stem-cell maintenance in the central nervous system, and also regulates gene expression in the stomach. Mutations in this gene have been associated with optic nerve hypoplasia and with syndromic microphthalmia, a severe form of structural eye malformation. This gene lies within an intron of another gene called SOX2 overlapping transcript (SOX2OT). [provided by RefSeq, Jul 2008]

SOX2 links:

SOX2-OT (HGNC:20209): (SOX2 overlapping transcript) This gene produces alternatively spliced long non-coding RNAs. These RNAs were observed to be upregulated in tumor cells and positively correlated to expression of the SRY-box 2 gene. Overexpression of these transcripts may promote cell proliferation. [provided by RefSeq, Dec 2017]

SOX2-OT links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 3-181712350-A-C is Benign according to our data. Variant chr3-181712350-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 678529.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003106.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SOX2	NM_003106.4	MANE Select	c.-11A>C	5_prime_UTR	Exon 1 of 1	NP_003097.1	P48431
SOX2-OT	NR_004053.3		n.768-2835A>C	intron	N/A
SOX2-OT	NR_075089.1		n.767+12467A>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SOX2	ENST00000325404.3	TSL:6 MANE Select	c.-11A>C	5_prime_UTR	Exon 1 of 1	ENSP00000323588.1	P48431
SOX2-OT	ENST00000466034.7	TSL:1	n.349+12467A>C	intron	N/A
SOX2-OT	ENST00000476964.6	TSL:1	n.482-27219A>C	intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000236

AC:

AN:

1270840

Hom.:

Cov.:

AF XY:

0.00000161

AC XY:

AN XY:

621060

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25304

American (AMR)

AF:

0.00

AC:

AN:

18576

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18222

East Asian (EAS)

AF:

0.00

AC:

AN:

30564

South Asian (SAS)

AF:

0.00

AC:

AN:

63746

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35340

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3716

European-Non Finnish (NFE)

AF:

0.00000293

AC:

AN:

1023924

Other (OTH)

AF:

0.00

AC:

AN:

51448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

1.1

PromoterAI

0.055

Neutral

(source)

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

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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