2-97189215-A-C

Variant names:

• chr2-97189215-A-C
• rs113372597
• NM_001354587.1:c.2173-3A>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001354587.1(ANKRD36):​c.2173-3A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (44 hom., cov: 15)
  • Exomes 𝑓: 0.0012 (305 hom.)
• Consequence: ANKRD36 NM_001354587.1 splice_region, intron
• Scores: Splicing: ADA: 0.00004899
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.321

Genes affected

ANKRD36 (HGNC:24079): (ankyrin repeat domain 36)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 2-97189215-A-C is Benign according to our data. Variant chr2-97189215-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2651163.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00119 (792/666302) while in subpopulation MID AF= 0.0243 (81/3334). AF 95% confidence interval is 0.02. There are 305 homozygotes in gnomad4_exome. There are 436 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD36	NM_001354587.1	c.2173-3A>C		splice_region_variant, intron_variant	Intron 33 of 75	ENST00000420699.9	NP_001341516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD36	ENST00000420699.9	c.2173-3A>C		splice_region_variant, intron_variant	Intron 33 of 75	5	NM_001354587.1	ENSP00000391950.4
ANKRD36	ENST00000461153.7	c.2173-3A>C		splice_region_variant, intron_variant	Intron 33 of 74	5		ENSP00000419530.3
ANKRD36	ENST00000652721.1	c.2173-3A>C		splice_region_variant, intron_variant	Intron 33 of 75			ENSP00000498611.1

Frequencies

GnomAD3 genomes AF: 0.00132 AC: 117 AN: 88876 Hom.: 44 Cov.: 15

Gnomad AFR AF: 0.000313

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00363

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000884

Gnomad SAS AF: 0.000505

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00202

Gnomad OTH AF: 0.00396

GnomAD3 exomes AF: 0.000771 AC: 103 AN: 133530 Hom.: 32 AF XY: 0.000738 AC XY: 53 AN XY: 71834

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000546

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00145

Gnomad OTH exome AF: 0.00162

GnomAD4 exome AF: 0.00119 AC: 792 AN: 666302 Hom.: 305 Cov.: 0 AF XY: 0.00129 AC XY: 436 AN XY: 338688

Gnomad4 AFR exome AF: 0.000504

Gnomad4 AMR exome AF: 0.00151

Gnomad4 ASJ exome AF: 0.0000614

Gnomad4 EAS exome AF: 0.0000277

Gnomad4 SAS exome AF: 0.000378

Gnomad4 FIN exome AF: 0.000125

Gnomad4 NFE exome AF: 0.00131

Gnomad4 OTH exome AF: 0.00184

GnomAD4 genome AF: 0.00131 AC: 117 AN: 89008 Hom.: 44 Cov.: 15 AF XY: 0.00149 AC XY: 65 AN XY: 43538

Gnomad4 AFR AF: 0.000312

Gnomad4 AMR AF: 0.00362

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000887

Gnomad4 SAS AF: 0.000505

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00202

Gnomad4 OTH AF: 0.00390

Alfa AF: 0.00101 Hom.: 5

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ANKRD36: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.93
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000049
dbscSNV1_RF	Benign	0.020
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: rs113372597; hg19: chr2-97854952;