NM_001242809.2:c.88A>C

Variant names:

• chr6-89567064-A-C
• NM_001242809.2:c.88A>C

Variant summary

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

The NM_001242809.2(ANKRD6):​c.88A>C​(p.Ile30Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANKRD6 NM_001242809.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.86
• Publications: 0 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]

ENSG00000237027 (HGNC:40804):

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242809.2. 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
	ANKRD6	NM_001242809.2	MANE Select	c.88A>C	p.Ile30Leu	missense	Exon 2 of 16	NP_001229738.1	Q9Y2G4-2
	ANKRD6	NM_001242811.1		c.88A>C	p.Ile30Leu	missense	Exon 2 of 16	NP_001229740.1	Q9Y2G4-2
	ANKRD6	NM_014942.4		c.88A>C	p.Ile30Leu	missense	Exon 2 of 16	NP_055757.3	Q9Y2G4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD6	ENST00000339746.9	TSL:1 MANE Select	c.88A>C	p.Ile30Leu	missense	Exon 2 of 16	ENSP00000345767.4	Q9Y2G4-2
	ANKRD6	ENST00000447838.6	TSL:1	c.88A>C	p.Ile30Leu	missense	Exon 2 of 16	ENSP00000396771.2	Q9Y2G4-3
	ANKRD6	ENST00000369408.9	TSL:1	c.88A>C	p.Ile30Leu	missense	Exon 2 of 15	ENSP00000358416.5	Q9Y2G4-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0047	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.35	N
PhyloP100		8.9
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.28
Sift	Benign	0.14	T
Sift4G	Benign	0.22	T
Polyphen		1.0	D
Vest4		0.73
MutPred		0.66		Loss of MoRF binding (P = 0.1174)
MVP		0.51
MPC		0.22
ClinPred		0.85	D
GERP RS		5.9
PromoterAI		-0.027	Neutral
Varity_R		0.17
gMVP		0.48
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

hg19: chr6-90276783;