2-157544202-ATTTTTTTTTTT-ATTTTTTTTTT

Variant names:

• chr2-157544202-AT-A
• rs765521635
• NM_145259.3:c.943+242delA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_145259.3(ACVR1C):​c.943+242delA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0082 (4 hom., cov: 25)
  • Failed GnomAD Quality Control
• Consequence: ACVR1C NM_145259.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 0 publications found

Genes affected

ACVR1C (HGNC:18123): (activin A receptor type 1C) ACVR1C is a type I receptor for the TGFB (see MIM 190180) family of signaling molecules. Upon ligand binding, type I receptors phosphorylate cytoplasmic SMAD transcription factors, which then translocate to the nucleus and interact directly with DNA or in complex with other transcription factors (Bondestam et al., 2001 [PubMed 12063393]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145259.3. 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
	ACVR1C	NM_145259.3	MANE Select	c.943+242delA		intron	N/A	NP_660302.2	Q8NER5-1
	ACVR1C	NM_001111031.2		c.793+242delA		intron	N/A	NP_001104501.1	Q8NER5-4
	ACVR1C	NM_001111032.2		c.703+242delA		intron	N/A	NP_001104502.1	Q8NER5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR1C	ENST00000243349.13	TSL:1 MANE Select	c.943+242delA		intron	N/A	ENSP00000243349.7	Q8NER5-1
	ACVR1C	ENST00000409680.7	TSL:1	c.793+242delA		intron	N/A	ENSP00000387168.3	Q8NER5-4
	ACVR1C	ENST00000335450.7	TSL:1	c.703+242delA		intron	N/A	ENSP00000335178.7	Q8NER5-3

Frequencies

GnomAD3 genomes AF: 0.00820 AC: 959 AN: 116956 Hom.: 4 Cov.: 25

Gnomad AFR AF: 0.00555

Gnomad AMI AF: 0.00254

Gnomad AMR AF: 0.00591

Gnomad ASJ AF: 0.000689

Gnomad EAS AF: 0.00720

Gnomad SAS AF: 0.00873

Gnomad FIN AF: 0.00681

Gnomad MID AF: 0.0135

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.00723

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00818 AC: 957 AN: 116926 Hom.: 4 Cov.: 25 AF XY: 0.00831 AC XY: 465 AN XY: 55956

African (AFR) AF: 0.00551 AC: 169 AN: 30652

American (AMR) AF: 0.00582 AC: 66 AN: 11340

Ashkenazi Jewish (ASJ) AF: 0.000689 AC: 2 AN: 2904

East Asian (EAS) AF: 0.00723 AC: 30 AN: 4148

South Asian (SAS) AF: 0.00878 AC: 33 AN: 3758

European-Finnish (FIN) AF: 0.00681 AC: 38 AN: 5584

Middle Eastern (MID) AF: 0.0150 AC: 3 AN: 200

European-Non Finnish (NFE) AF: 0.0108 AC: 603 AN: 56026

Other (OTH) AF: 0.00720 AC: 11 AN: 1528

Alfa AF: 0.000686 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.2
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: rs765521635; hg19: chr2-158400714; COSMIC: COSV54647850;