9-38586206-G-C

Position:

• chr9-38586206-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000399703.6(ANKRD18A):​c.2224C>G​(p.Leu742Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD18A ENST00000399703.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39

Genes affected

ANKRD18A (HGNC:23643): (ankyrin repeat domain 18A)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13769463).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD18A	NM_147195.4	c.2224C>G	p.Leu742Val	missense_variant	12/16	ENST00000399703.6	NP_671728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD18A	ENST00000399703.6	c.2224C>G	p.Leu742Val	missense_variant	12/16	1	NM_147195.4	ENSP00000382610	A2
ANKRD18A	ENST00000602295.5	c.394C>G	p.Leu132Val	missense_variant	4/8	1		ENSP00000473463
ANKRD18A	ENST00000703205.1	c.2410C>G	p.Leu804Val	missense_variant	14/18			ENSP00000515234	P2
ANKRD18A	ENST00000703204.1	c.*1184C>G		3_prime_UTR_variant, NMD_transcript_variant	9/17			ENSP00000515233

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.86e-7 AC: 1 AN: 1457230 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724526

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 06, 2023

The c.2224C>G (p.L742V) alteration is located in exon 12 (coding exon 12) of the ANKRD18A gene. This alteration results from a C to G substitution at nucleotide position 2224, causing the leucine (L) at amino acid position 742 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0088	.;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.76	.;N
REVEL	Benign	0.057
Sift	Benign	0.26	.;T
Sift4G	Uncertain	0.055	T;D
Polyphen		0.88	.;P
Vest4		0.069
MutPred		0.34		.;Loss of stability (P = 0.0429);
MVP		0.15
MPC		0.12
ClinPred		0.30	T
GERP RS		0.34
Varity_R		0.10
gMVP		0.014

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-38586203;