2-95921626-A-G

Variant names:

• chr2-95921626-A-G
• rs200558089
• NM_001393982.1:c.2226T>C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001393982.1(ANKRD36C):​c.2226T>C​(p.Asp742Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,608,760 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (5 hom., cov: 30)
  • Exomes 𝑓: 0.00083 (3 hom.)
• Consequence: ANKRD36C NM_001393982.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.239

Genes affected

ANKRD36C (HGNC:32946): (ankyrin repeat domain 36C)

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 2-95921626-A-G is Benign according to our data. Variant chr2-95921626-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2651133.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.239 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD36C	NM_001393982.1	c.2226T>C	p.Asp742Asp	synonymous_variant	Exon 34 of 88	ENST00000295246.7	NP_001380911.1
ANKRD36C	NM_001310154.3	c.2301T>C	p.Asp767Asp	synonymous_variant	Exon 35 of 89		NP_001297083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD36C	ENST00000295246.7	c.2226T>C	p.Asp742Asp	synonymous_variant	Exon 34 of 88	5	NM_001393982.1	ENSP00000295246.7
ANKRD36C	ENST00000456556.5	c.2226T>C	p.Asp742Asp	synonymous_variant	Exon 34 of 67	5		ENSP00000403302.1
ANKRD36C	ENST00000534304.5	n.*554T>C		non_coding_transcript_exon_variant	Exon 16 of 43	5		ENSP00000433685.1
ANKRD36C	ENST00000534304.5	n.*554T>C		3_prime_UTR_variant	Exon 16 of 43	5		ENSP00000433685.1

Frequencies

GnomAD3 genomes AF: 0.00310 AC: 469 AN: 151502 Hom.: 5 Cov.: 30

Gnomad AFR AF: 0.00571

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000694

Gnomad OTH AF: 0.00384

GnomAD3 exomes AF: 0.00133 AC: 325 AN: 243474 Hom.: 0 AF XY: 0.00122 AC XY: 161 AN XY: 132300

Gnomad AFR exome AF: 0.00478

Gnomad AMR exome AF: 0.00368

Gnomad ASJ exome AF: 0.00423

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000231

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000574

Gnomad OTH exome AF: 0.00288

GnomAD4 exome AF: 0.000832 AC: 1213 AN: 1457140 Hom.: 3 Cov.: 31 AF XY: 0.000822 AC XY: 596 AN XY: 724808

Gnomad4 AFR exome AF: 0.00617

Gnomad4 AMR exome AF: 0.00327

Gnomad4 ASJ exome AF: 0.00442

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000198

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000532

Gnomad4 OTH exome AF: 0.00198

GnomAD4 genome AF: 0.00309 AC: 468 AN: 151620 Hom.: 5 Cov.: 30 AF XY: 0.00351 AC XY: 260 AN XY: 74092

Gnomad4 AFR AF: 0.00567

Gnomad4 AMR AF: 0.0111

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000694

Gnomad4 OTH AF: 0.00380

Alfa AF: 0.00201 Hom.: 0

Bravo AF: 0.00380

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ANKRD36C: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.72
DANN	Benign	0.20

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: rs200558089; hg19: chr2-96587374;