10-111004836-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_007373.4(SHOC2):c.1161+42T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 1,367,102 control chromosomes in the GnomAD database, including 463,055 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). The gene SHOC2 is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.83 ( 52240 hom., cov: 31)

Exomes 𝑓: 0.82 ( 410815 hom. )

Consequence

SHOC2
NM_007373.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.02

Publications

15 publications found

Variant links:

Genes affected

SHOC2 (HGNC:15454): (SHOC2 leucine rich repeat scaffold protein) This gene encodes a protein that consists almost entirely of leucine-rich repeats, a domain implicated in protein-protein interactions. The protein may function as a scaffold linking RAS to downstream signal transducers in the RAS/ERK MAP kinase signaling cascade. Mutations in this gene have been associated with Noonan-like syndrome with loose anagen hair. [provided by RefSeq, May 2010]

SHOC2 Gene-Disease associations (from GenCC):

Noonan syndrome-like disorder with loose anagen hair
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Noonan syndrome-like disorder with loose anagen hair 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, 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
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Noonan syndrome with multiple lentigines
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

SHOC2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_007373.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Specifications for SHOC2 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 10-111004836-T-C is Benign according to our data. Variant chr10-111004836-T-C is described in ClinVar as Benign. ClinVar VariationId is 41450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007373.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SHOC2	NM_007373.4	MANE Select	c.1161+42T>C	intron	N/A	NP_031399.2
SHOC2	NM_001324336.2		c.1161+42T>C	intron	N/A	NP_001311265.1	Q9UQ13-1
SHOC2	NM_001324337.2		c.1161+42T>C	intron	N/A	NP_001311266.1	Q9UQ13-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SHOC2	ENST00000369452.9	TSL:1 MANE Select	c.1161+42T>C	intron	N/A	ENSP00000358464.5	Q9UQ13-1
SHOC2	ENST00000685059.1		c.1161+42T>C	intron	N/A	ENSP00000510210.1	Q9UQ13-1
SHOC2	ENST00000688928.1		c.1161+42T>C	intron	N/A	ENSP00000509273.1	Q9UQ13-1

Frequencies

GnomAD3 genomes

AF:

0.828

AC:

125912

AN:

152064

Hom.:

52217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.830

Gnomad AMI

AF:

0.757

Gnomad AMR

AF:

0.880

Gnomad ASJ

AF:

0.851

Gnomad EAS

AF:

0.847

Gnomad SAS

AF:

0.815

Gnomad FIN

AF:

0.820

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.816

Gnomad OTH

AF:

0.815

GnomAD2 exomes

AF:

0.836

AC:

191454

AN:

228946

AF XY:

0.833

show subpopulations

Gnomad AFR exome

AF:

0.831

Gnomad AMR exome

AF:

0.923

Gnomad ASJ exome

AF:

0.846

Gnomad EAS exome

AF:

0.844

Gnomad FIN exome

AF:

0.817

Gnomad NFE exome

AF:

0.815

Gnomad OTH exome

AF:

0.828

GnomAD4 exome

AF:

0.822

AC:

999103

AN:

1214920

Hom.:

410815

Cov.:

AF XY:

0.822

AC XY:

505960

AN XY:

615354

show subpopulations

African (AFR)

AF:

0.834

AC:

23977

AN:

28748

American (AMR)

AF:

0.917

AC:

39523

AN:

43092

Ashkenazi Jewish (ASJ)

AF:

0.845

AC:

20694

AN:

24500

East Asian (EAS)

AF:

0.862

AC:

33111

AN:

38430

South Asian (SAS)

AF:

0.823

AC:

65934

AN:

80082

European-Finnish (FIN)

AF:

0.814

AC:

40397

AN:

49644

Middle Eastern (MID)

AF:

0.818

AC:

4237

AN:

5178

European-Non Finnish (NFE)

AF:

0.815

AC:

728202

AN:

893070

Other (OTH)

AF:

0.825

AC:

43028

AN:

52176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

9904

19807

29711

39614

49518

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15464

30928

46392

61856

77320

<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:

0.828

AC:

125982

AN:

152182

Hom.:

52240

Cov.:

AF XY:

0.828

AC XY:

61626

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.830

AC:

34429

AN:

41496

American (AMR)

AF:

0.880

AC:

13475

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.851

AC:

2947

AN:

3464

East Asian (EAS)

AF:

0.847

AC:

4391

AN:

5182

South Asian (SAS)

AF:

0.815

AC:

3923

AN:

4814

European-Finnish (FIN)

AF:

0.820

AC:

8689

AN:

10592

Middle Eastern (MID)

AF:

0.786

AC:

231

AN:

294

European-Non Finnish (NFE)

AF:

0.816

AC:

55502

AN:

68008

Other (OTH)

AF:

0.807

AC:

1705

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1111

2223

3334

4446

5557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

884

1768

2652

3536

4420

<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:

0.823

Hom.:

29986

Bravo

AF:

0.831

Asia WGS

AF:

0.790

AC:

2749

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Noonan syndrome-like disorder with loose anagen hair 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.65

(source)

DANN

Benign

0.65

PhyloP100

-1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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