rs79727992

Variant names:

• chr21-36719771-G-A
• rs79727992
• NM_005069.6:c.349-50G>A

Your query was ambiguous. Multiple possible variants found:

• chr21-36719771-G-A
• chr21-36719771-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005069.6(SIM2):​c.349-50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 1,156,442 control chromosomes in the GnomAD database, including 978 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 0.032 (105 hom., cov: 32)
  • Exomes 𝑓: 0.038 (873 hom.)
• Consequence: SIM2 NM_005069.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.53
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0515 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIM2	NM_005069.6	MANE Select	c.349-50G>A		intron	N/A	NP_005060.1
	SIM2	NM_009586.5		c.349-50G>A		intron	N/A	NP_033664.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIM2	ENST00000290399.11	TSL:1 MANE Select	c.349-50G>A		intron	N/A	ENSP00000290399.6
	SIM2	ENST00000431229.1	TSL:1	c.160-50G>A		intron	N/A	ENSP00000392003.1
	SIM2	ENST00000483178.2	TSL:3	c.58-50G>A		intron	N/A	ENSP00000476273.1

Frequencies

GnomAD3 genomes AF: 0.0324 AC: 4924 AN: 152114 Hom.: 105 Cov.: 32

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0336

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.0559

Gnomad FIN AF: 0.0329

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0379

Gnomad OTH AF: 0.0465

GnomAD2 exomes AF: 0.0351 AC: 8689 AN: 247774 AF XY: 0.0367

Gnomad AFR exome AF: 0.0190

Gnomad AMR exome AF: 0.0237

Gnomad ASJ exome AF: 0.0440

Gnomad EAS exome AF: 0.00267

Gnomad FIN exome AF: 0.0320

Gnomad NFE exome AF: 0.0403

Gnomad OTH exome AF: 0.0387

GnomAD4 exome AF: 0.0380 AC: 38204 AN: 1004210 Hom.: 873 Cov.: 13 AF XY: 0.0391 AC XY: 20266 AN XY: 518766

African (AFR) AF: 0.0182 AC: 446 AN: 24548

American (AMR) AF: 0.0247 AC: 1087 AN: 43990

Ashkenazi Jewish (ASJ) AF: 0.0433 AC: 1002 AN: 23138

East Asian (EAS) AF: 0.0237 AC: 890 AN: 37476

South Asian (SAS) AF: 0.0529 AC: 4075 AN: 77094

European-Finnish (FIN) AF: 0.0318 AC: 1686 AN: 52946

Middle Eastern (MID) AF: 0.0501 AC: 177 AN: 3532

European-Non Finnish (NFE) AF: 0.0390 AC: 27155 AN: 696398

Other (OTH) AF: 0.0374 AC: 1686 AN: 45088

GnomAD4 genome AF: 0.0324 AC: 4929 AN: 152232 Hom.: 105 Cov.: 32 AF XY: 0.0325 AC XY: 2422 AN XY: 74434

African (AFR) AF: 0.0212 AC: 881 AN: 41554

American (AMR) AF: 0.0336 AC: 513 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 170 AN: 3470

East Asian (EAS) AF: 0.0108 AC: 56 AN: 5166

South Asian (SAS) AF: 0.0553 AC: 267 AN: 4826

European-Finnish (FIN) AF: 0.0329 AC: 349 AN: 10618

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0379 AC: 2574 AN: 67996

Other (OTH) AF: 0.0460 AC: 97 AN: 2110

Alfa AF: 0.0372 Hom.: 120

Bravo AF: 0.0305

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.032
DANN	Benign	0.65
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs79727992; hg19: chr21-38092072;