rs6454764

chr6-89601247-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.220-1782T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,004 control chromosomes in the GnomAD database, including 54,501 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 0.84 (54501 hom., cov: 30)
• Consequence: ANKRD6 NM_001242809.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD6	NM_001242809.2	c.220-1782T>C		intron_variant		ENST00000339746.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD6	ENST00000339746.9	c.220-1782T>C		intron_variant		1	NM_001242809.2	A1

Frequencies

GnomAD3 genomes AF: 0.836 AC: 126942 AN: 151886 Hom.: 54499 Cov.: 30

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.953

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.889

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.929

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.950

Gnomad OTH AF: 0.852

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

GnomAD4 genome AF: 0.835 AC: 126981 AN: 152004 Hom.: 54501 Cov.: 30 AF XY: 0.832 AC XY: 61870 AN XY: 74322

Gnomad4 AFR AF: 0.635

Gnomad4 AMR AF: 0.821

Gnomad4 ASJ AF: 0.889

Gnomad4 EAS AF: 0.741

Gnomad4 SAS AF: 0.810

Gnomad4 FIN AF: 0.929

Gnomad4 NFE AF: 0.950

Gnomad4 OTH AF: 0.851

Alfa AF: 0.930 Hom.: 139687

Bravo AF: 0.820

Asia WGS AF: 0.766 AC: 2664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	2.5
Dann	Benign	0.35

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: rs6454764; hg19: chr6-90310966;