5-65225009-CC-TT

Variant names:

• chr5-65225009-CC-TT
• NM_197941.4:c.2105_2106delGGinsAA
• ADAMTS6 p.Arg702Lys

Variant summary

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

The NM_197941.4(ADAMTS6):​c.2105_2106delGGinsAA​(p.Arg702Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADAMTS6 NM_197941.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.89
• Publications: 0 publications found

Genes affected

ADAMTS6 (HGNC:222): (ADAM metallopeptidase with thrombospondin type 1 motif 6) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature enzyme. Expression of this gene may be regulated by the cytokine TNF-alpha. [provided by RefSeq, Mar 2016]

ADAMTS6 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_197941.4. 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
	ADAMTS6	NM_197941.4	MANE Select	c.2105_2106delGGinsAA	p.Arg702Lys	missense	N/A	NP_922932.2	Q9UKP5-1
	ADAMTS6	NR_135689.2		n.3113_3114delGGinsAA		non_coding_transcript_exon	Exon 18 of 26

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS6	ENST00000381055.8	TSL:1 MANE Select	c.2105_2106delGGinsAA	p.Arg702Lys	missense	N/A	ENSP00000370443.3	Q9UKP5-1
	ADAMTS6	ENST00000470597.5	TSL:1	n.1984_1985delGGinsAA		non_coding_transcript_exon	Exon 15 of 18
	ADAMTS6	ENST00000381052.8	TSL:2	n.*1377_*1378delGGinsAA		non_coding_transcript_exon	Exon 18 of 26	ENSP00000424377.1	Q9UKP5-4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9

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.

Other links and lift over

hg19: chr5-64520836;