chr9-104102152-C-T

Variant names:

• chr9-104102152-C-T
• rs61755103
• NM_006444.3:c.829C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_006444.3(SMC2):​c.829C>T​(p.Leu277Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000771 in 1,577,210 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (6 hom.)
• Consequence: SMC2 NM_006444.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.63
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0064918995).
• BP6: Variant 9-104102152-C-T is Benign according to our data. Variant chr9-104102152-C-T is described in ClinVar as Benign. ClinVar VariationId is 739502.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 629 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006444.3. 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	NM_006444.3	MANE Select	c.829C>T	p.Leu277Phe	missense	Exon 8 of 25	NP_006435.2	O95347-1
	SMC2	NM_001042550.2		c.829C>T	p.Leu277Phe	missense	Exon 8 of 25	NP_001036015.1	O95347-1
	SMC2	NM_001042551.2		c.829C>T	p.Leu277Phe	missense	Exon 8 of 25	NP_001036016.1	O95347-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMC2	ENST00000374793.8	TSL:1 MANE Select	c.829C>T	p.Leu277Phe	missense	Exon 8 of 25	ENSP00000363925.3	O95347-1
	SMC2	ENST00000286398.11	TSL:1	c.829C>T	p.Leu277Phe	missense	Exon 8 of 25	ENSP00000286398.7	O95347-1
	SMC2	ENST00000374787.7	TSL:2	c.829C>T	p.Leu277Phe	missense	Exon 8 of 25	ENSP00000363919.3	O95347-1

Frequencies

GnomAD3 genomes AF: 0.00414 AC: 629 AN: 151888 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000722

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: 0.0000588

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00101 AC: 248 AN: 244654 AF XY: 0.000708

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.000297

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000449

Gnomad OTH exome AF: 0.000337

GnomAD4 exome AF: 0.000412 AC: 587 AN: 1425206 Hom.: 6 Cov.: 29 AF XY: 0.000350 AC XY: 249 AN XY: 710594

African (AFR) AF: 0.0158 AC: 510 AN: 32286

American (AMR) AF: 0.000503 AC: 22 AN: 43700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25782

East Asian (EAS) AF: 0.00 AC: 0 AN: 39396

South Asian (SAS) AF: 0.0000477 AC: 4 AN: 83916

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53044

Middle Eastern (MID) AF: 0.000365 AC: 2 AN: 5474

European-Non Finnish (NFE) AF: 0.0000120 AC: 13 AN: 1082570

Other (OTH) AF: 0.000610 AC: 36 AN: 59038

GnomAD4 genome AF: 0.00414 AC: 629 AN: 152004 Hom.: 10 Cov.: 32 AF XY: 0.00389 AC XY: 289 AN XY: 74308

African (AFR) AF: 0.0147 AC: 611 AN: 41450

American (AMR) AF: 0.000721 AC: 11 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67978

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.00224 Hom.: 4

Bravo AF: 0.00461

ESP6500AA AF: 0.0121 AC: 53

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00115 AC: 139

Asia WGS AF: 0.000867 AC: 3 AN: 3474

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0065	T
MetaSVM	Uncertain	0.23	D
MutationAssessor	Uncertain	2.9	M
PhyloP100		4.6
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.29
Sift	Benign	0.041	D
Sift4G	Uncertain	0.039	D
Polyphen		0.76	P
Vest4		0.71
MVP		0.61
MPC		0.34
ClinPred		0.065	T
GERP RS		5.8
Varity_R		0.70
gMVP		0.38
Mutation Taster		=100/0	polymorphism

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: rs61755103; hg19: chr9-106864433;