rs144391749

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006939.4(SOS2):c.3075+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00972 in 1,309,156 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0075 ( 2 hom., cov: 32)

Exomes 𝑓: 0.010 ( 82 hom. )

Consequence

SOS2
NM_006939.4 splice_region, intron

Scores

Splicing: ADA: 0.0001460

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.276

Publications

1 publications found

Variant links:

Genes affected

SOS2 (HGNC:11188): (SOS Ras/Rho guanine nucleotide exchange factor 2) This gene encodes a regulatory protein that is involved in the positive regulation of ras proteins. Mutations in this gene are associated with Noonan Syndrome-9. [provided by RefSeq, Jul 2016]

SOS2 Gene-Disease associations (from GenCC):

Noonan syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
Noonan syndrome 9
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics, Genomics England PanelApp
cardiofaciocutaneous syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Costello syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Noonan syndrome with multiple lentigines
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Noonan syndrome-like disorder with loose anagen hair
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

SOS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 14-50134116-G-A is Benign according to our data. Variant chr14-50134116-G-A is described in ClinVar as Benign. ClinVar VariationId is 384712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.01 (11588/1156932) while in subpopulation MID AF = 0.0228 (118/5184). AF 95% confidence interval is 0.0194. There are 82 homozygotes in GnomAdExome4. There are 5895 alleles in the male GnomAdExome4 subpopulation. Median coverage is 16. This position passed quality control check.

BS2

High AC in GnomAd4 at 1138 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006939.4. 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
	SOS2	NM_006939.4	MANE Select	c.3075+7C>T		splice_region intron	N/A	NP_008870.2	Q07890-1
	SOS2	NM_001411020.1		c.2976+7C>T		splice_region intron	N/A	NP_001397949.1	Q07890-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SOS2	ENST00000216373.10	TSL:1 MANE Select	c.3075+7C>T	splice_region intron	N/A	ENSP00000216373.5	Q07890-1
SOS2	ENST00000543680.5	TSL:1	c.2976+7C>T	splice_region intron	N/A	ENSP00000445328.1	Q07890-2
SOS2	ENST00000934708.1		c.3216+7C>T	splice_region intron	N/A	ENSP00000604767.1

Frequencies

GnomAD3 genomes

AF:

0.00749

AC:

1139

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00208

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00622

Gnomad FIN

AF:

0.00623

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.0167

GnomAD2 exomes

AF:

0.00849

AC:

2070

AN:

243826

AF XY:

0.00905

show subpopulations

Gnomad AFR exome

AF:

0.00173

Gnomad AMR exome

AF:

0.00753

Gnomad ASJ exome

AF:

0.0121

Gnomad EAS exome

AF:

0.0000555

Gnomad FIN exome

AF:

0.00815

Gnomad NFE exome

AF:

0.0113

Gnomad OTH exome

AF:

0.0120

GnomAD4 exome

AF:

0.0100

AC:

11588

AN:

1156932

Hom.:

Cov.:

AF XY:

0.00999

AC XY:

5895

AN XY:

590082

show subpopulations

African (AFR)

AF:

0.00173

AC:

AN:

27186

American (AMR)

AF:

0.00824

AC:

348

AN:

42256

Ashkenazi Jewish (ASJ)

AF:

0.0110

AC:

266

AN:

24132

East Asian (EAS)

AF:

0.00

AC:

AN:

38142

South Asian (SAS)

AF:

0.00718

AC:

556

AN:

77448

European-Finnish (FIN)

AF:

0.00794

AC:

423

AN:

53280

Middle Eastern (MID)

AF:

0.0228

AC:

118

AN:

5184

European-Non Finnish (NFE)

AF:

0.0111

AC:

9318

AN:

839102

Other (OTH)

AF:

0.0102

AC:

512

AN:

50202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

525

1049

1574

2098

2623

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

294

588

882

1176

1470

<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

AF:

0.00748

AC:

1138

AN:

152224

Hom.:

Cov.:

AF XY:

0.00724

AC XY:

539

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.00207

AC:

AN:

41542

American (AMR)

AF:

0.0111

AC:

169

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0127

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00622

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00623

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0103

AC:

699

AN:

67996

Other (OTH)

AF:

0.0166

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

118

177

236

295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0103

Hom.:

Bravo

AF:

0.00792

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0128

EpiControl

AF:

0.0141

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Noonan syndrome 9 (3)

not specified (2)

Noonan syndrome and Noonan-related syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.99

(source)

DANN

Benign

0.59

PhyloP100

-0.28

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00015

dbscSNV1_RF

Benign

0.0080

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over