dbSNP rs10519324: TMOD2:c.284-84C>T (chr15-51773628-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_014548.4(TMOD2):c.284-84C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00643 in 1,403,874 control chromosomes in the GnomAD database, including 41 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 0.0092 ( 15 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 26 hom. )

Consequence

TMOD2
NM_014548.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.111

Publications

4 publications found

Variant links:

Genes affected

TMOD2 (HGNC:11872): (tropomodulin 2) This gene encodes a neuronal-specific member of the tropomodulin family of actin-regulatory proteins. The encoded protein caps the pointed end of actin filaments preventing both elongation and depolymerization. The capping activity of this protein is dependent on its association with tropomyosin. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Dec 2008]

TMOD2 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=-0.72).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00921 (1403/152288) while in subpopulation AFR AF = 0.0185 (767/41562). AF 95% confidence interval is 0.0174. There are 15 homozygotes in GnomAd4. There are 636 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMOD2	NM_014548.4 link	c.284-84C>T		intron_variant	Intron 3 of 9	ENST00000249700.9	NP_055363.1	Q9NZR1-1
TMOD2	NM_001142885.2 link	c.284-84C>T		intron_variant	Intron 3 of 8		NP_001136357.1	Q9NZR1-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMOD2	ENST00000249700.9 link	c.284-84C>T	intron_variant	Intron 3 of 9	1	NM_014548.4	ENSP00000249700.4	Q9NZR1-1
TMOD2	ENST00000435126.6 link	c.284-84C>T	intron_variant	Intron 3 of 8	2		ENSP00000404590.2	Q9NZR1-2
TMOD2	ENST00000539962.6 link	c.152-84C>T	intron_variant	Intron 4 of 10	2		ENSP00000437743.2	G5EA42
TMOD2	ENST00000560576.1 link	n.796+6558C>T	intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.00921

AC:

1402

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0185

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00366

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00642

Gnomad FIN

AF:

0.00820

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00650

Gnomad OTH

AF:

0.00719

GnomAD4 exome

AF:

0.00609

AC:

7620

AN:

1251586

Hom.:

AF XY:

0.00606

AC XY:

3763

AN XY:

620964

show subpopulations

African (AFR)

AF:

0.0183

AC:

504

AN:

27534

American (AMR)

AF:

0.00321

AC:

AN:

26502

Ashkenazi Jewish (ASJ)

AF:

0.000434

AC:

AN:

18428

East Asian (EAS)

AF:

0.0000560

AC:

AN:

35730

South Asian (SAS)

AF:

0.00438

AC:

287

AN:

65496

European-Finnish (FIN)

AF:

0.00752

AC:

338

AN:

44920

Middle Eastern (MID)

AF:

0.00264

AC:

AN:

4922

European-Non Finnish (NFE)

AF:

0.00621

AC:

6070

AN:

976804

Other (OTH)

AF:

0.00611

AC:

313

AN:

51250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

349

698

1048

1397

1746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

232

464

696

928

1160

<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:

0.00921

AC:

1403

AN:

152288

Hom.:

Cov.:

AF XY:

0.00854

AC XY:

636

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0185

AC:

767

AN:

41562

American (AMR)

AF:

0.00366

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00820

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00650

AC:

442

AN:

68016

Other (OTH)

AF:

0.00712

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

142

212

283

354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00877

Hom.:

Bravo

AF:

0.00901

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.5

(source)

DANN

Benign

0.74

PhyloP100

-0.11

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over