rs2820223

Variant names:

• chr6-35041518-T-C
• rs2820223
• NM_015245.3:c.2011-12581T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015245.3(ANKS1A):​c.2011-12581T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,092 control chromosomes in the GnomAD database, including 13,846 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 0.38 (13846 hom., cov: 32)
• Consequence: ANKS1A NM_015245.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 6 publications found

Genes affected

ANKS1A (HGNC:20961): (ankyrin repeat and sterile alpha motif domain containing 1A) Predicted to enable ephrin receptor binding activity. Predicted to be involved in ephrin receptor signaling pathway; neuron remodeling; and substrate-dependent cell migration. Predicted to act upstream of or within negative regulation of ubiquitin-dependent protein catabolic process and regulation of ephrin receptor signaling pathway. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286550 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS1A	NM_015245.3	c.2011-12581T>C		intron_variant	Intron 11 of 23	ENST00000360359.5	NP_056060.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKS1A	ENST00000360359.5	c.2011-12581T>C		intron_variant	Intron 11 of 23	1	NM_015245.3	ENSP00000353518.3
ENSG00000286550	ENST00000660796.1	n.569A>G		non_coding_transcript_exon_variant	Exon 2 of 2
ANKS1A	ENST00000649117.1	c.2074-12581T>C		intron_variant	Intron 12 of 24			ENSP00000497393.1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58375 AN: 151974 Hom.: 13842 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.384 AC: 58362 AN: 152092 Hom.: 13846 Cov.: 32 AF XY: 0.390 AC XY: 28976 AN XY: 74352

African (AFR) AF: 0.106 AC: 4390 AN: 41526

American (AMR) AF: 0.438 AC: 6691 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1370 AN: 3470

East Asian (EAS) AF: 0.276 AC: 1429 AN: 5178

South Asian (SAS) AF: 0.465 AC: 2241 AN: 4822

European-Finnish (FIN) AF: 0.590 AC: 6219 AN: 10538

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34401 AN: 67972

Other (OTH) AF: 0.380 AC: 802 AN: 2108

Alfa AF: 0.439 Hom.: 2912

Bravo AF: 0.359

Asia WGS AF: 0.323 AC: 1120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.79
PhyloP100		-0.092
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2820223; hg19: chr6-35009295;