chr2-97154693-C-T

Variant names:

• chr2-97154693-C-T
• rs776281681
• NM_001354587.1:c.1212C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001354587.1(ANKRD36):​c.1212C>T​(p.Asp404Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0068 (2 hom., cov: 26)
  • Exomes 𝑓: 0.000063 (15 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD36 NM_001354587.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.08
• Publications: 1 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 2-97154693-C-T is Benign according to our data. Variant chr2-97154693-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2651160.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.08 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354587.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD36	NM_001354587.1	MANE Select	c.1212C>T	p.Asp404Asp	synonymous	Exon 15 of 76	NP_001341516.1	A6QL64-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD36	ENST00000420699.9	TSL:5 MANE Select	c.1212C>T	p.Asp404Asp	synonymous	Exon 15 of 76	ENSP00000391950.4	A6QL64-1
	ANKRD36	ENST00000461153.7	TSL:5	c.1212C>T	p.Asp404Asp	synonymous	Exon 15 of 75	ENSP00000419530.3	A6QL64-1
	ANKRD36	ENST00000652721.1		c.1212C>T	p.Asp404Asp	synonymous	Exon 15 of 76	ENSP00000498611.1	A6QL64-1

Frequencies

GnomAD3 genomes AF: 0.00677 AC: 621 AN: 91674 Hom.: 2 Cov.: 26

Gnomad AFR AF: 0.00364

Gnomad AMI AF: 0.00542

Gnomad AMR AF: 0.00655

Gnomad ASJ AF: 0.00338

Gnomad EAS AF: 0.00733

Gnomad SAS AF: 0.00645

Gnomad FIN AF: 0.0161

Gnomad MID AF: 0.0104

Gnomad NFE AF: 0.00784

Gnomad OTH AF: 0.00610

GnomAD2 exomes AF: 0.000902 AC: 123 AN: 136418 AF XY: 0.000342

Gnomad AFR exome AF: 0.000133

Gnomad AMR exome AF: 0.0000832

Gnomad ASJ exome AF: 0.000243

Gnomad EAS exome AF: 0.000392

Gnomad FIN exome AF: 0.000635

Gnomad NFE exome AF: 0.00201

Gnomad OTH exome AF: 0.000490

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000628 AC: 83 AN: 1321826 Hom.: 15 Cov.: 30 AF XY: 0.0000829 AC XY: 54 AN XY: 651766

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000645 AC: 2 AN: 31000

American (AMR) AF: 0.000118 AC: 4 AN: 33922

Ashkenazi Jewish (ASJ) AF: 0.0000412 AC: 1 AN: 24256

East Asian (EAS) AF: 0.0000869 AC: 3 AN: 34504

South Asian (SAS) AF: 0.0000390 AC: 3 AN: 76834

European-Finnish (FIN) AF: 0.00121 AC: 37 AN: 30568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5606

European-Non Finnish (NFE) AF: 0.0000301 AC: 31 AN: 1029682

Other (OTH) AF: 0.0000361 AC: 2 AN: 55454

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000000380807), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00679 AC: 623 AN: 91710 Hom.: 2 Cov.: 26 AF XY: 0.00956 AC XY: 384 AN XY: 40148

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00368 AC: 93 AN: 25304

American (AMR) AF: 0.00665 AC: 61 AN: 9176

Ashkenazi Jewish (ASJ) AF: 0.00338 AC: 8 AN: 2366

East Asian (EAS) AF: 0.00704 AC: 23 AN: 3268

South Asian (SAS) AF: 0.00613 AC: 17 AN: 2774

European-Finnish (FIN) AF: 0.0161 AC: 76 AN: 4712

Middle Eastern (MID) AF: 0.0112 AC: 2 AN: 178

European-Non Finnish (NFE) AF: 0.00787 AC: 331 AN: 42056

Other (OTH) AF: 0.00681 AC: 9 AN: 1322

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.135 Hom.: 140

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.43
DANN	Benign	0.19
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs776281681; hg19: chr2-97820430; COSMIC: COSV70742939;