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6-89612325-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001242809.2(ANKRD6):c.471G>A(p.Thr157=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000725 in 1,566,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00076 ( 0 hom. )

Consequence

ANKRD6
NM_001242809.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.31
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-89612325-G-A is Benign according to our data. Variant chr6-89612325-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3046684.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.31 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANKRD6NM_001242809.2 linkuse as main transcriptc.471G>A p.Thr157= synonymous_variant 6/16 ENST00000339746.9
LOC124901359XR_007059673.1 linkuse as main transcriptn.206-6394C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANKRD6ENST00000339746.9 linkuse as main transcriptc.471G>A p.Thr157= synonymous_variant 6/161 NM_001242809.2 A1Q9Y2G4-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000355
AC:
54
AN:
152232
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000661
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000350
AC:
62
AN:
177264
Hom.:
0
AF XY:
0.000382
AC XY:
36
AN XY:
94282
show subpopulations
Gnomad AFR exome
AF:
0.000416
Gnomad AMR exome
AF:
0.0000373
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000156
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000115
Gnomad NFE exome
AF:
0.000721
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000765
AC:
1081
AN:
1413954
Hom.:
0
Cov.:
31
AF XY:
0.000736
AC XY:
514
AN XY:
698620
show subpopulations
Gnomad4 AFR exome
AF:
0.000279
Gnomad4 AMR exome
AF:
0.0000530
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000539
Gnomad4 SAS exome
AF:
0.0000125
Gnomad4 FIN exome
AF:
0.0000398
Gnomad4 NFE exome
AF:
0.000942
Gnomad4 OTH exome
AF:
0.000699
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000354
AC:
54
AN:
152350
Hom.:
0
Cov.:
33
AF XY:
0.000322
AC XY:
24
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.000216
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000661
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000686
Hom.:
0
Bravo
AF:
0.000329

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

ANKRD6-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesApr 09, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
Cadd
Benign
0.11
Dann
Benign
0.92

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs377367109; hg19: chr6-90322044; API