dbSNP rs10512326: SMC2:c.-1750G>A (chr9-104092264-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000603487.1(SMC2-DT):n.211C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,046 control chromosomes in the GnomAD database, including 8,086 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 0.31 ( 8086 hom., cov: 32)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

SMC2-DT
ENST00000603487.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.243

Publications

4 publications found

Variant links:

COSMIC-nc: COSV53956416

Genes affected

SMC2 (HGNC:14011): (structural maintenance of chromosomes 2) Predicted to enable ATP binding activity; chromatin binding activity; and single-stranded DNA binding activity. Involved in mitotic chromosome condensation. Located in condensed chromosome; cytoplasm; and nuclear lumen. Part of condensin complex. [provided by Alliance of Genome Resources, Apr 2022]

SMC2 links:

SMC2-DT (HGNC:50827): (SMC2 divergent transcript)

SMC2-DT links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000603487.1, 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

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000603487.1. 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
	SMC2-DT	NR_121580.1		n.211C>T		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
SMC2-DT	ENST00000603487.1	TSL:2	n.211C>T	non_coding_transcript_exon	Exon 1 of 3
SMC2-DT	ENST00000773587.1		n.64C>T	non_coding_transcript_exon	Exon 1 of 2
SMC2-DT	ENST00000603949.1	TSL:6	n.*138C>T	downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.306

AC:

46492

AN:

151924

Hom.:

8087

Cov.:

show subpopulations

Gnomad AFR

AF:

0.222

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.427

Gnomad ASJ

AF:

0.307

Gnomad EAS

AF:

0.767

Gnomad SAS

AF:

0.424

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.329

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.306

AC:

46498

AN:

152042

Hom.:

8086

Cov.:

AF XY:

0.312

AC XY:

23173

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.222

AC:

9186

AN:

41470

American (AMR)

AF:

0.428

AC:

6535

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.307

AC:

1066

AN:

3468

East Asian (EAS)

AF:

0.767

AC:

3958

AN:

5160

South Asian (SAS)

AF:

0.423

AC:

2043

AN:

4826

European-Finnish (FIN)

AF:

0.261

AC:

2760

AN:

10560

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.295

AC:

20061

AN:

67962

Other (OTH)

AF:

0.328

AC:

693

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1573

3146

4720

6293

7866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

464

928

1392

1856

2320

<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:

0.316

Hom.:

1333

Bravo

AF:

0.317

Asia WGS

AF:

0.554

AC:

1929

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.4

(source)

DANN

Benign

0.22

PhyloP100

-0.24

Splicing

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

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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