Genetic Variant NM_001253845.2:c.*1885T>C (chr22-50484788-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001253845.2(ADM2):c.*1885T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 152,026 control chromosomes in the GnomAD database, including 39,547 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 0.72 ( 39522 hom., cov: 32)

Exomes 𝑓: 0.61 ( 25 hom. )

Consequence

ADM2
NM_001253845.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.54

Publications

6 publications found

Variant links:

Genes affected

ADM2 (HGNC:28898): (adrenomedullin 2) This gene encodes a member of the calcitonin gene-related peptide (CGRP)/calcitonin family of hormones that play a role in the regulation of cardiovascular homeostasis, prolactin release, anti-diuresis, anti-natriuresis, and regulation of food and water intake. The encoded protein is proteolytically processed to generate one or more biologically active peptides. [provided by RefSeq, Jul 2015]

ADM2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001253845.2. 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
	ADM2	NM_001253845.2	MANE Select	c.*1885T>C		3_prime_UTR	Exon 3 of 3	NP_001240774.1	Q7Z4H4
	ADM2	NM_001369882.1		c.*1885T>C		3_prime_UTR	Exon 2 of 2	NP_001356811.1	Q7Z4H4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADM2	ENST00000395737.2	TSL:1 MANE Select	c.*1885T>C		3_prime_UTR	Exon 3 of 3	ENSP00000379086.1	Q7Z4H4
	ADM2	ENST00000395738.2	TSL:1	c.*1885T>C		3_prime_UTR	Exon 2 of 2	ENSP00000379087.2	Q7Z4H4

Frequencies

GnomAD3 genomes

AF:

0.716

AC:

108681

AN:

151786

Hom.:

39481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.813

Gnomad AMI

AF:

0.813

Gnomad AMR

AF:

0.668

Gnomad ASJ

AF:

0.520

Gnomad EAS

AF:

0.912

Gnomad SAS

AF:

0.716

Gnomad FIN

AF:

0.764

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.657

Gnomad OTH

AF:

0.669

GnomAD4 exome

AF:

0.607

AC:

AN:

122

Hom.:

Cov.:

AF XY:

0.659

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.631

AC:

AN:

Other (OTH)

AF:

0.400

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.716

AC:

108778

AN:

151904

Hom.:

39522

Cov.:

AF XY:

0.720

AC XY:

53484

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.813

AC:

33639

AN:

41388

American (AMR)

AF:

0.667

AC:

10185

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.520

AC:

1803

AN:

3470

East Asian (EAS)

AF:

0.912

AC:

4707

AN:

5162

South Asian (SAS)

AF:

0.716

AC:

3449

AN:

4816

European-Finnish (FIN)

AF:

0.764

AC:

8062

AN:

10550

Middle Eastern (MID)

AF:

0.585

AC:

172

AN:

294

European-Non Finnish (NFE)

AF:

0.657

AC:

44611

AN:

67936

Other (OTH)

AF:

0.672

AC:

1417

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1521

3043

4564

6086

7607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

836

1672

2508

3344

4180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.664

Hom.:

45657

Bravo

AF:

0.716

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

1.7

(source)

DANN

Benign

0.27

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over