6-89589491-T-C

Position:

• chr6-89589491-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001242809.2(ANKRD6):​c.121-6425T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.974 in 152,294 control chromosomes in the GnomAD database, including 72,390 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.97 (72390 hom., cov: 31)
• Consequence: ANKRD6 NM_001242809.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258

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:):

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD6	NM_001242809.2	c.121-6425T>C		intron_variant		ENST00000339746.9	NP_001229738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD6	ENST00000339746.9	c.121-6425T>C		intron_variant		1	NM_001242809.2	ENSP00000345767.4

Frequencies

GnomAD3 genomes AF: 0.974 AC: 148285 AN: 152176 Hom.: 72353 Cov.: 31

Gnomad AFR AF: 0.912

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.988

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.982

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

GnomAD4 genome AF: 0.974 AC: 148379 AN: 152294 Hom.: 72390 Cov.: 31 AF XY: 0.975 AC XY: 72611 AN XY: 74454

Gnomad4 AFR AF: 0.912

Gnomad4 AMR AF: 0.988

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.983

Alfa AF: 0.985 Hom.: 8612

Bravo AF: 0.971

Asia WGS AF: 0.993 AC: 3453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs6939321; hg19: chr6-90299210;