6-89606052-C-T

Variant names:

• chr6-89606052-C-T
• rs16881983
• NM_001242809.2:c.364C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001242809.2(ANKRD6):​c.364C>T​(p.Gln122*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 1,443,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: ANKRD6 NM_001242809.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57
• Publications: 8 publications found

Genes affected

ANKRD6 (HGNC:17280): (ankyrin repeat domain 6) Predicted to be involved in negative regulation of canonical Wnt signaling pathway and positive regulation of JNK cascade. Predicted to act upstream of or within positive regulation of Wnt signaling pathway, planar cell polarity pathway. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

LYRM2 (HGNC:25229): (LYR motif containing 2)

LOC124901359 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD6	NM_001242809.2	c.364C>T	p.Gln122*	stop_gained	Exon 5 of 16	ENST00000339746.9	NP_001229738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD6	ENST00000339746.9	c.364C>T	p.Gln122*	stop_gained	Exon 5 of 16	1	NM_001242809.2	ENSP00000345767.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000446 AC: 1 AN: 224118 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000991

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000111 AC: 16 AN: 1443866 Hom.: 0 Cov.: 28 AF XY: 0.00000838 AC XY: 6 AN XY: 716190

African (AFR) AF: 0.0000301 AC: 1 AN: 33214

American (AMR) AF: 0.00 AC: 0 AN: 42572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25700

East Asian (EAS) AF: 0.00 AC: 0 AN: 39108

South Asian (SAS) AF: 0.00 AC: 0 AN: 82374

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.0000136 AC: 15 AN: 1103070

Other (OTH) AF: 0.00 AC: 0 AN: 59710

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 47

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	43
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.98
FATHMM_MKL	Pathogenic	0.98	D
PhyloP100		7.6
Vest4		0.50
GERP RS		5.0
Mutation Taster		=11/189	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs16881983; hg19: chr6-90315771; COSMIC: COSV60230858; COSMIC: COSV60230858;