rs948602

Variant names:

• chr18-47903874-T-A
• rs948602
• NM_005901.6:c.-53-7065A>T

Your query was ambiguous. Multiple possible variants found:

• chr18-47903874-T-A
• chr18-47903874-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005901.6(SMAD2):​c.-53-7065A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.58 (8423 hom., cov: 7)
• Consequence: SMAD2 NM_005901.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.514

Genes affected

SMAD2 (HGNC:6768): (SMAD family member 2) The protein encoded by this gene belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein mediates the signal of the transforming growth factor (TGF)-beta, and thus regulates multiple cellular processes, such as cell proliferation, apoptosis, and differentiation. This protein is recruited to the TGF-beta receptors through its interaction with the SMAD anchor for receptor activation (SARA) protein. In response to TGF-beta signal, this protein is phosphorylated by the TGF-beta receptors. The phosphorylation induces the dissociation of this protein with SARA and the association with the family member SMAD4. The association with SMAD4 is important for the translocation of this protein into the nucleus, where it binds to target promoters and forms a transcription repressor complex with other cofactors. This protein can also be phosphorylated by activin type 1 receptor kinase, and mediates the signal from the activin. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAD2	NM_005901.6	c.-53-7065A>T		intron_variant	Intron 1 of 10	ENST00000262160.11	NP_005892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMAD2	ENST00000262160.11	c.-53-7065A>T		intron_variant	Intron 1 of 10	1	NM_005901.6	ENSP00000262160.6

Frequencies

GnomAD3 genomes AF: 0.582 AC: 34094 AN: 58620 Hom.: 8432 Cov.: 7

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.584

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.581 AC: 34073 AN: 58596 Hom.: 8423 Cov.: 7 AF XY: 0.578 AC XY: 15410 AN XY: 26662

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.582

Asia WGS AF: 0.472 AC: 1275 AN: 2700

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.62

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: rs948602; hg19: chr18-45430245;