16-67648677-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001013838.3(CARMIL2):c.1440-8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0783 in 1,601,826 control chromosomes in the GnomAD database, including 9,627 homozygotes. 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 Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 3188 hom., cov: 32)

Exomes 𝑓: 0.071 ( 6439 hom. )

Consequence

CARMIL2
NM_001013838.3 splice_region, intron

Scores

Splicing: ADA: 0.00001198

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.225

Publications

27 publications found

Variant links:

Genes affected

CARMIL2 (HGNC:27089): (capping protein regulator and myosin 1 linker 2) This gene encodes a member of the CARMIL (capping protein, Arp2/3, myosin-I linker) family of proteins. The encoded protein interacts with and negatively regulates the heterodimeric capping protein and promotes cell migration. Reduced expression of this gene has been observed in human psoriasis patients. Mutations in this gene cause a human immunodeficiency syndrome characterized by smooth muscle tumors and impaired T-cell function. [provided by RefSeq, May 2017]

CARMIL2 Gene-Disease associations (from GenCC):

severe combined immunodeficiency due to CARMIL2 deficiency
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet

CARMIL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-67648677-T-C is Benign according to our data. Variant chr16-67648677-T-C is described in ClinVar as Benign. ClinVar VariationId is 1166790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013838.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CARMIL2	NM_001013838.3	MANE Select	c.1440-8T>C	splice_region intron	N/A	NP_001013860.1
CARMIL2	NM_001438835.1		c.1332-8T>C	splice_region intron	N/A	NP_001425764.1
CARMIL2	NM_001438244.1		c.1332-8T>C	splice_region intron	N/A	NP_001425173.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CARMIL2	ENST00000334583.11	TSL:1 MANE Select	c.1440-8T>C	splice_region intron	N/A	ENSP00000334958.5
CARMIL2	ENST00000545661.5	TSL:1	c.1332-8T>C	splice_region intron	N/A	ENSP00000441481.1
CARMIL2	ENST00000602321.5	TSL:2	n.716T>C	non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22529

AN:

152042

Hom.:

3173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.374

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0943

Gnomad ASJ

AF:

0.0899

Gnomad EAS

AF:

0.00328

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.0360

Gnomad MID

AF:

0.242

Gnomad NFE

AF:

0.0552

Gnomad OTH

AF:

0.133

GnomAD2 exomes

AF:

0.0857

AC:

19627

AN:

229068

AF XY:

0.0873

show subpopulations

Gnomad AFR exome

AF:

0.372

Gnomad AMR exome

AF:

0.0533

Gnomad ASJ exome

AF:

0.0912

Gnomad EAS exome

AF:

0.00234

Gnomad FIN exome

AF:

0.0368

Gnomad NFE exome

AF:

0.0590

Gnomad OTH exome

AF:

0.0790

GnomAD4 exome

AF:

0.0709

AC:

102829

AN:

1449666

Hom.:

6439

Cov.:

AF XY:

0.0729

AC XY:

52500

AN XY:

720058

show subpopulations

African (AFR)

AF:

0.396

AC:

13124

AN:

33106

American (AMR)

AF:

0.0565

AC:

2437

AN:

43158

Ashkenazi Jewish (ASJ)

AF:

0.0943

AC:

2442

AN:

25900

East Asian (EAS)

AF:

0.00138

AC:

AN:

39038

South Asian (SAS)

AF:

0.161

AC:

13525

AN:

84000

European-Finnish (FIN)

AF:

0.0386

AC:

2014

AN:

52156

Middle Eastern (MID)

AF:

0.154

AC:

886

AN:

5754

European-Non Finnish (NFE)

AF:

0.0570

AC:

63029

AN:

1106598

Other (OTH)

AF:

0.0887

AC:

5318

AN:

59956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

4324

8648

12972

17296

21620

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2612

5224

7836

10448

13060

<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:

0.148

AC:

22577

AN:

152160

Hom.:

3188

Cov.:

AF XY:

0.146

AC XY:

10872

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.374

AC:

15517

AN:

41480

American (AMR)

AF:

0.0941

AC:

1440

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0899

AC:

312

AN:

3470

East Asian (EAS)

AF:

0.00329

AC:

AN:

5174

South Asian (SAS)

AF:

0.157

AC:

756

AN:

4826

European-Finnish (FIN)

AF:

0.0360

AC:

382

AN:

10608

Middle Eastern (MID)

AF:

0.236

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0552

AC:

3755

AN:

67988

Other (OTH)

AF:

0.131

AC:

277

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

851

1702

2552

3403

4254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

224

448

672

896

1120

<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:

0.0790

Hom.:

1815

Bravo

AF:

0.157

Asia WGS

AF:

0.105

AC:

366

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Severe combined immunodeficiency due to CARMIL2 deficiency

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.9

(source)

DANN

Benign

0.47

PhyloP100

0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.030

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over