chr6-89595923-G-A

Variant names:

• chr6-89595923-G-A
• rs745644433
• NM_001242809.2:c.128G>A

Variant summary

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

The NM_001242809.2(ANKRD6):​c.128G>A​(p.Arg43Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000386 in 1,607,078 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000041 (0 hom.)
• Consequence: ANKRD6 NM_001242809.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.36
• 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]

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

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.128G>A	p.Arg43Gln	missense	Exon 3 of 16	NP_001229738.1	Q9Y2G4-2
	ANKRD6	NM_001242811.1		c.128G>A	p.Arg43Gln	missense	Exon 3 of 16	NP_001229740.1	Q9Y2G4-2
	ANKRD6	NM_014942.4		c.128G>A	p.Arg43Gln	missense	Exon 3 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.128G>A	p.Arg43Gln	missense	Exon 3 of 16	ENSP00000345767.4	Q9Y2G4-2
	ANKRD6	ENST00000447838.6	TSL:1	c.128G>A	p.Arg43Gln	missense	Exon 3 of 16	ENSP00000396771.2	Q9Y2G4-3
	ANKRD6	ENST00000369408.9	TSL:1	c.128G>A	p.Arg43Gln	missense	Exon 3 of 15	ENSP00000358416.5	Q9Y2G4-1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152114 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000126 AC: 3 AN: 238584 AF XY: 0.00000775

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000573

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000185

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000406 AC: 59 AN: 1454964 Hom.: 0 Cov.: 30 AF XY: 0.0000332 AC XY: 24 AN XY: 722910

African (AFR) AF: 0.00 AC: 0 AN: 33394

American (AMR) AF: 0.00 AC: 0 AN: 43904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25924

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39542

South Asian (SAS) AF: 0.00 AC: 0 AN: 84420

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000505 AC: 56 AN: 1108866

Other (OTH) AF: 0.0000333 AC: 2 AN: 60142

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152114 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74302

African (AFR) AF: 0.00 AC: 0 AN: 41400

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000248 AC: 3

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	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.012	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.0	L
PhyloP100		9.4
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.45
Sift	Benign	0.032	D
Sift4G	Benign	0.082	T
Polyphen		1.0	D
Vest4		0.82
MutPred		0.60		Loss of MoRF binding (P = 0.0239)
MVP		0.86
MPC		0.36
ClinPred		0.81	D
GERP RS		5.8
Varity_R		0.26
gMVP		0.68
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
SpliceAI score (max)		0.070		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: rs745644433; hg19: chr6-90305642;