dbSNP rs78455239: SIM2:c.457+29C>A (chr21-36719958-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005069.6(SIM2):c.457+29C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000307 in 1,303,142 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

SIM2
NM_005069.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.584

Publications

1 publications found

Variant links:

Genes affected

SIM2 (HGNC:10883): (SIM bHLH transcription factor 2) This gene represents a homolog of the Drosophila single-minded (sim) gene, which encodes a transcription factor that is a master regulator of neurogenesis. The encoded protein is ubiquitinated by RING-IBR-RING-type E3 ubiquitin ligases, including the parkin RBR E3 ubiquitin protein ligase. This gene maps within the so-called Down syndrome chromosomal region, and is thus thought to contribute to some specific Down syndrome phenotypes. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2014]

SIM2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020127058).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005069.6. 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
	SIM2	NM_005069.6	MANE Select	c.457+29C>A		intron	N/A	NP_005060.1	Q14190-1
	SIM2	NM_009586.5		c.457+29C>A		intron	N/A	NP_033664.2	Q14190-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SIM2	ENST00000290399.11	TSL:1 MANE Select	c.457+29C>A		intron	N/A	ENSP00000290399.6	Q14190-1
SIM2	ENST00000431229.1	TSL:1	c.268+29C>A		intron	N/A	ENSP00000392003.1	H7BZX8
SIM2	ENST00000483178.2	TSL:3	c.195C>A	p.Asn65Lys	missense	Exon 2 of 2	ENSP00000476273.1	V9GY04

Frequencies

GnomAD3 genomes

AF:

0.000153

AC:

AN:

150162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000544

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000486

GnomAD2 exomes

AF:

0.0000331

AC:

AN:

241726

AF XY:

0.0000305

show subpopulations

Gnomad AFR exome

AF:

0.000505

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000147

AC:

AN:

1152884

Hom.:

Cov.:

AF XY:

0.00000851

AC XY:

AN XY:

587402

show subpopulations

African (AFR)

AF:

0.000646

AC:

AN:

26316

American (AMR)

AF:

0.00

AC:

AN:

42526

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23994

East Asian (EAS)

AF:

0.00

AC:

AN:

38414

South Asian (SAS)

AF:

0.00

AC:

AN:

79570

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46694

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5112

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

840180

Other (OTH)

AF:

0.00

AC:

AN:

50078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.407

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

AF:

0.000153

AC:

AN:

150258

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

AN XY:

73360

show subpopulations

African (AFR)

AF:

0.000543

AC:

AN:

40546

American (AMR)

AF:

0.00

AC:

AN:

15168

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4768

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10226

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67652

Other (OTH)

AF:

0.000481

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.536

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000189

ExAC

AF:

0.0000330

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.2

(source)

DANN

Benign

0.73

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.18

MetaRNN

Benign

0.020

PhyloP100

0.58

Sift4G

Benign

0.13

MVP

0.33

GERP RS

3.3

Mutation Taster

=100/0

polymorphism

(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

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