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2-189676766-T-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001378068.1(ANKAR):c.276T>G(p.Thr92=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,614,160 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0093 ( 21 hom., cov: 32)
Exomes 𝑓: 0.0010 ( 36 hom. )

Consequence

ANKAR
NM_001378068.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.835
Variant links:
Genes affected
ANKAR (HGNC:26350): (ankyrin and armadillo repeat containing) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

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=-0.89).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-189676766-T-G is Benign according to our data. Variant chr2-189676766-T-G is described in ClinVar as [Benign]. Clinvar id is 775795.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=-0.835 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00933 (1422/152342) while in subpopulation AFR AF= 0.0327 (1360/41578). AF 95% confidence interval is 0.0313. There are 21 homozygotes in gnomad4. There are 669 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 21 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANKARNM_001378068.1 linkuse as main transcriptc.276T>G p.Thr92= synonymous_variant 2/23 ENST00000684021.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANKARENST00000684021.1 linkuse as main transcriptc.276T>G p.Thr92= synonymous_variant 2/23 NM_001378068.1 P1Q7Z5J8-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00930
AC:
1415
AN:
152224
Hom.:
21
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0326
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00275
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:
0.0000882
Gnomad OTH
AF:
0.00716
GnomAD3 exomes
AF:
0.00242
AC:
608
AN:
251012
Hom.:
12
AF XY:
0.00187
AC XY:
254
AN XY:
135710
show subpopulations
Gnomad AFR exome
AF:
0.0345
Gnomad AMR exome
AF:
0.00119
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000265
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.00102
AC:
1496
AN:
1461818
Hom.:
36
Cov.:
31
AF XY:
0.000865
AC XY:
629
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.0370
Gnomad4 AMR exome
AF:
0.00141
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.00286
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00933
AC:
1422
AN:
152342
Hom.:
21
Cov.:
32
AF XY:
0.00898
AC XY:
669
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.0327
Gnomad4 AMR
AF:
0.00268
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00709
Alfa
AF:
0.00414
Hom.:
5
Bravo
AF:
0.0107
Asia WGS
AF:
0.00318
AC:
11
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 14, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
Cadd
Benign
1.7
Dann
Benign
0.58

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

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

Other links and lift over

dbSNP: rs77970584; hg19: chr2-190541492; API