9-104098498-A-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_006444.3(SMC2):c.371A>C(p.Asn124Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00679 in 1,598,840 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0070 (46 hom.)
• Consequence: SMC2 NM_006444.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.05

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00913018).
• BP6: Variant 9-104098498-A-C is Benign according to our data. Variant chr9-104098498-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 787626.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 670 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMC2	NM_006444.3	c.371A>C	p.Asn124Thr	missense_variant	4/25	ENST00000374793.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMC2	ENST00000374793.8	c.371A>C	p.Asn124Thr	missense_variant	4/25	1	NM_006444.3	P1
SMC2	ENST00000286398.11	c.371A>C	p.Asn124Thr	missense_variant	4/25	1		P1
SMC2	ENST00000374787.7	c.371A>C	p.Asn124Thr	missense_variant	4/25	2		P1
SMC2	ENST00000440179.5	c.-65A>C		5_prime_UTR_variant	2/6	3

Frequencies

GnomAD3 genomes AF: 0.00440 AC: 670 AN: 152170 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00536

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00704

Gnomad OTH AF: 0.00766

GnomAD3 exomes AF: 0.00413 AC: 979 AN: 236794 Hom.: 2 AF XY: 0.00428 AC XY: 549 AN XY: 128250

Gnomad AFR exome AF: 0.00137

Gnomad AMR exome AF: 0.00284

Gnomad ASJ exome AF: 0.00122

Gnomad EAS exome AF: 0.0000581

Gnomad SAS exome AF: 0.000801

Gnomad FIN exome AF: 0.000750

Gnomad NFE exome AF: 0.00717

Gnomad OTH exome AF: 0.00634

GnomAD4 exome AF: 0.00704 AC: 10186 AN: 1446552 Hom.: 46 Cov.: 28 AF XY: 0.00689 AC XY: 4958 AN XY: 719436

Gnomad4 AFR exome AF: 0.00129

Gnomad4 AMR exome AF: 0.00273

Gnomad4 ASJ exome AF: 0.000889

Gnomad4 EAS exome AF: 0.0000258

Gnomad4 SAS exome AF: 0.00102

Gnomad4 FIN exome AF: 0.000999

Gnomad4 NFE exome AF: 0.00860

Gnomad4 OTH exome AF: 0.00559

GnomAD4 genome AF: 0.00440 AC: 670 AN: 152288 Hom.: 2 Cov.: 33 AF XY: 0.00411 AC XY: 306 AN XY: 74472

Gnomad4 AFR AF: 0.00197

Gnomad4 AMR AF: 0.00536

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00705

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00643 Hom.: 5

Bravo AF: 0.00481

TwinsUK AF: 0.0113 AC: 42

ALSPAC AF: 0.0114 AC: 44

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00791 AC: 68

ExAC AF: 0.00437 AC: 530

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 03, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.27
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.40	T;T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D;.;.
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.0091	T;T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	2.0	M;M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.5	D;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.0030	D;D;D
Sift4G	Benign	0.49	T;T;T
Polyphen		0.29	B;B;B
Vest4		0.37
MVP		0.60
MPC		0.14
ClinPred		0.027	T
GERP RS		5.8
Varity_R		0.67
gMVP		0.72

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

LitVar

Other links and lift over

dbSNP: rs61755310; hg19: chr9-106860779; COSMIC: COSV105140892;