18-12095529-G-C

Position:

• chr18-12095529-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_001277333.2(ANKRD62):​c.426G>C​(p.Leu142Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000311 in 1,561,506 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 0.00038 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (0 hom.)
• Consequence: ANKRD62 NM_001277333.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.980

Genes affected

ANKRD62 (HGNC:35241): (ankyrin repeat domain 62)

ANKRD62 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 18-12095529-G-C is Benign according to our data. Variant chr18-12095529-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 932552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.98 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD62	NM_001277333.2	c.426G>C	p.Leu142Leu	synonymous_variant	3/14	ENST00000587848.3	NP_001264262.1
ANKRD62	XR_001753188.2	n.601G>C		non_coding_transcript_exon_variant	3/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD62	ENST00000587848.3	c.426G>C	p.Leu142Leu	synonymous_variant	3/14	5	NM_001277333.2	ENSP00000467740.2

Frequencies

GnomAD3 genomes AF: 0.000381 AC: 58 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000598 AC: 103 AN: 172146 Hom.: 0 AF XY: 0.000597 AC XY: 56 AN XY: 93802

Gnomad AFR exome AF: 0.000814

Gnomad AMR exome AF: 0.000510

Gnomad ASJ exome AF: 0.00452

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000120

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000450

Gnomad OTH exome AF: 0.00102

GnomAD4 exome AF: 0.000304 AC: 428 AN: 1409232 Hom.: 0 Cov.: 31 AF XY: 0.000315 AC XY: 220 AN XY: 697662

Gnomad4 AFR exome AF: 0.000917

Gnomad4 AMR exome AF: 0.000493

Gnomad4 ASJ exome AF: 0.00435

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000855

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000184

Gnomad4 OTH exome AF: 0.000745

GnomAD4 genome AF: 0.000381 AC: 58 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27 AN XY: 74442

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000869 Hom.: 0

Bravo AF: 0.000559

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.84
DANN	Benign	0.62

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: rs779671539; hg19: chr18-12095528;